OBJECTIVE： To investigate the clinical efficacy and safety of rh-endostatin combined with cantharidin sodium vitamin B6 in the treatment of advanced non-small cell lung cancer （NSCLC）. METHODS： 180 patients diagnosed as advanced NSCLC were divided into group A， group B  and group C ， with 60 cases in each group according to random number table method. 3 groups were all given gemcitabine+cisplatin （GP） chemotherapy plan； Group B additionally received Rh-endostatin injection 7.5 mg/m2 intravenously for 3 h， d1-14；  group C was additionally given Cantharidin sodium vitamin B6 injection 40 ml intravenously， qd， d1-14， on the basis of group B. every 21 days for a cycle， evaluation of therapeutic effect after 2 cycles. The clinical benefit rate， quality improvement rate of life， time to progression （TTP） and the occurrence of ADR were observed in 3 groups. RESULTS： The clinical benefit rate of groups A， B and C were 40.0％， 58.3％， 71.6％ respectively， the quality improvement rate of life in 3 groups were 28.3％， 41.7％， 56.7％ respectively， the differences were statistically significant among those groups （P＜0.05）. The median TTP of groups A， B and C were 126， 190 and 195 days， TTP of groups B and C were significantly longer than that of group A， with statistical significance （P＜0.05）； there was no significant difference between group B and group C（P＞0.05）. The rates of leukopenia， thrombocytopenia， nausea and vomiting in group C were significantly lower than those of group A and B， with statistical significance （P＜0.05）； there was no statistical significance between group A and B （P＞0.05）. CONCLUSIONS： Rh-endostatin combined with cantharidin sodium vitamin B6 can significantly improve the effectiveness of chemotherapy in patients with advanced NSCLC on the basis of the GP chemotherapy， while reduce the toxicity of chemotherapy drugs， improve the quality of life and prolong the survival time.