BACKGROUND: Unresectable hepatocellular carcinoma (HCC) lacks effective therapy and entails very poor pro- gress. In 1991, we found that Chinese herbal compound Star-99 has potentially effect on HCC. The purpose of this study was to probe the anti-cancer effect and the mecha- nism of focal injection of Chinese herbal compound Star-99 into HCC of mice. METHODS: In 32 nude mice transplanted with human he- patocellular carcinoma SMMC-7721, 16 received hypoder- mic implant and the other 16 orthotopic liver transplant. They were randomly divided into three groups: Star-99 group (Chinese herbal compound, 16 mice), alcohol group (8) and saline group (8), respectively. Intratumoral injec- tion of Star-99, alcohol and saline was carried out 10 days after transplantation of HCC. Twenty days after the first in- jection , the nude mice were killed after being injected eve- ry 5 days with a total of 4 injections in each mouse. Tumor tissues were examined pathologically or via an electron mi- croscope and flow cytometrical (FCM) DNA analysis. The three diameters of the tumor were measured with high-fre- quency ultrasound before and after injection, and the growth index was calculated with the following formula: volume of tumor (after treatment-before treatment)/vo- lume of tumor (before treatment). Double-blind method was applied in the experiment. RESULTS: The growth index of the Star-99 group (0.068± 0.022) and the alcohol group (0.07910.024) was markedly lower than that of the saline group (4.345±1.453, P< 0.01), but there was no significant difference between the Star-99 and alcohol groups. Coagulation (8/8) was the major pathological change in the alcohol group. In the Star-99 group, however, the phenomenon of lymphocytes attacking cancer cells could even be seen under the electron microscope. The typical apoptosis cells and apoptosis bo- dies as well as the collagen fibrae lined in mass could also be seen in the group (14/16). FCM DNA analysis showed that the rate of apoptosis in the Star-99 group (93.8%) was sig- nificantly higher than that in the alcohol (12.5%) and saline groups (12.5%) (P<0.01). CONCLUSIONS: This study shows that Star-99 markedly inhibits and destructs hepatocellular cancer cells. Star-99 is effective to directly destroy the membrane, cytoplasm and nuclei of tumor cells, causing their crumbling, activate the immune function and inflammatory reaction of nude mice, and induce the apoptosis of cancer cells. The effect of Star- 99 is significantly different from that of alcohol that mainly causes coagulation of cancer cells. Star-99 is feasible in the treatment of HCC. BACKGROUND: Unresectable hepatocellular carcinoma (HCC) lacks effective therapy and entails very poor pro-gress. In 1991, we found that Chinese herbal compound Star-99 has potentially effect on HCC. The purpose of this study was to probe the anti-cancer effect METHODS: In 32 nude mice transplanted with human hepatocellular carcinoma SMMC-7721, 16 received hypoder- mic implants and the other 16 orthotopic liver transplant They were randomly divided into three groups: Star-99 group (Chinese herbal compound, 16 mice), alcohol group (8) and saline group (8), respectively. Intratumoral injec tion of Star-99, alcohol and saline was carried Twenty days after the first in- jection, the nude mice were killed after being injected eve-ry 5 days with a total of 4 injections in each mouse. Tumor tissues were scanned pathologically or via an electron mi - crosco The three diameters of the tumor were measured with high-fre quency ultrasound before and after injection, and the growth index was calculated with the following formula: volume of tumor (after treatment-before treatment Double-blind method was applied in the experiment. RESULTS: The growth index of the Star-99 group (0.068 ± 0.022) and the alcohol group (0.07910.024) was markedly lower than that of the saline group (4.345 ± 1.453, P <0.01), but there was no significant difference between the Star-99 and alcohol groups. Coagulation (8/8) was the major pathological change in the alcohol group. -99 group, however, the phenomenon of lymphocytes attacking cancer cells could even be seen under the electron microscope. The typical apoptosis cells and apoptosis bo-dies as well as the collagen fibra lined in mass could also be seen in the group (14 / 16). FCM DNA analysis showed that the rate of apop tosis in the Star-99 group (93.8%) was sig nificantly higher than that in the alcohol (12.5%) and saline groups (12.5%) (P <0.01). CONCLUSIONS: This study shows that Star-99 markedly inhibits and destructs hepatocellular cancer cells. Star-99 is effective to directly destroy the membrane, cytoplasm and nuclei of tumor cells, causing their crumbling, activate the immune function and inflammatory reaction of nude mice, and induce the apoptosis of cancer cells. The effect of Star - 99 is significantly different from that of alcohol that predominantly coagulation of cancer cells. Star-99 is feasible in the treatment of HCC.