目的探讨新型基因工程人肿瘤坏死因子（ｎｒｈＴＮＦ）联合足叶乙甙（ＶＰ(１６)）的协同抗肿瘤作用及ｎｒｈＴＮＦ的毒副作用、方法以复制成功的Ｌｅｗｉｓ肺癌（３ＬＬ）小鼠为模型局部用药，观察用药后移植瘤的坏死范围、抑瘤率、肺转移瘤数及ｎｒｈＴＮＦ的毒副作用。结果ｎｒｈＴＮＦ或ＶＰ(１６)瘤体内注射均能使肿瘤出现一定程度坏死，肿瘤生长及肺转移受到一定的抑制，抑瘤率分别为３３．７％、３０．４６％，肺转移瘤数与对照组比较Ｐ＜０．０５。而联合用药，肿瘤出现广泛的出血坏死，能显著抑制肿瘤生长及肺转移，抑瘤率为６５．７７％，大于理论抑瘤率５３．９１％，肺转移瘤数与对照组比较Ｐ＜０．０１。同时观察到ｎｒｈＴＮＦ对实验小鼠无明显毒副作用。结论ｎｒｈＴＮＦ和Ｖ／Ｐ(１６)联合用药，具有协同抗肿瘤作用，ｎｒｈＴＮＦ瘤体内用药，毒副反应少，安全性高。 Objective To investigate the synergistic anti-tumor effect of a novel gene-engineered human tumor necrosis factor (nrhTNF) combined with etoposide (VP(16)) and the toxic side effects of nrhTNF, and to use locally replicated Lewis lung cancer (3LL) mice as a model for topical use. Observe the extent of necrosis, tumor inhibition rate, lung metastasis, and toxic side effects of nrhTNF after transplantation. Results Intratumoral injection of nrhTNF or VP(16) all caused tumor necrosis to a certain extent. Tumor growth and lung metastasis were inhibited. The tumor inhibition rates were 33.7% and 30.46%, respectively. Group comparison P<0.05. Combined use of drugs, the tumor appeared extensive hemorrhage and necrosis, can significantly inhibit tumor growth and lung metastasis, tumor inhibition rate was 65.77%, greater than the theoretical inhibition rate of 53.91%, lung metastasis compared with the control group P<0 .01. At the same time, it was observed that nrhTNF had no obvious side effects on the experimental mice. Conclusion The combined use of nrhTNF and V/P(16) has a synergistic anti-tumor effect. The nrhTNF tumor is used in vivo, with few side effects and high safety.