AIM: To block the adhesion of tumor cells to the extracellular matrix, and prevent tumor metastasis and recurfence, the dimer of the β peptide (DLYYLMDLSYSMKGGDLYYLMDLSYSMK, β2) was designed and synthesized and its anti-adhesion and anti-invasion effects on hepatocellular carcinoma cells were assessed. Additionally,its influence on the metastasis and recurrence of mouse hepatocellular carcinoma was measured.METHODS: The anti-adhesion effect of β2 on the highly metastatic hepatocellular carcinoma cell line HCCLM6 cells and fibronectin (FN) was assayed by the HTT assay. The inhibition of invasion of HCCLM6 cells by β2 was observed using a Transwell (modified Boyden chamber)and matrigel. Using the hepatocellular carcinoma metastasis model and LCI-D20 nude mice, the influence of β2 on the metastasis and recurrence of hepatocellular carcinoma after early resection was investigated.RESULTS: HCCLM6 cells co-incubated with 100 μmol/L,50 μmol/L, 20 μmol/L or 10 μmol/L β2 for 3 h showed an obvious decrease in adhesion to FN. The adhesion inhibition ratios were 11.8%, 21.7%, 29.6% and 48.7%,respectively. Additionally, HCCLM6 cells cultured with 100 μmol/L β2 had a dramatic decrease in cell invasion.β2 was also observed to inhibit the incisal edge recurfence and the distant metastasis of nude mice hepatocellular carcinoma after early resection (P ＜ 0.05).CONCLUSION: The β2 peptide can specifically block the adhesion and invasion of HCCLM6 cells, and can inhibit HCC recurrence and metastasis of LCI-D20 model posthepatectomy in vivo. Thus, β2 should be further studied as a new anti-tumor drug.