Abstract: Objective To investigate the therapeutic effect， long term survival and side effects on advanced gastric cancer patients treated with irinotecan（CPT-11） plus cisplatin（DDP） regimen and CPT-11 alone as secondline chemotherapy. Methods A total of 168 gastric cancer patients enrolled from June 2012 to January 2014 failed in firstline chemotherapy were randomly allocated to CPT-11+DDP group（CPT-11 250mg/m2 iv， d1； DDP 70 mg/m2 iv， d1， 21 days as a cycle） or CPT-11 group（250 mg/m2 iv，d1，21 days as a cycle） with 68 cases in each group. Short-term efficacy was evaluated after 2 cycles’ therapy， and long-term efficacy， as well as side effects was compared between both groups. Results Efficacy could be evaluated in 168 cases. In CPT-11+DDP group，there were 3 cases in CR， 11 in PR， 44 in SD， and the response rate（RR） and disease control rate（DCR） were 167% and 890%. In CPT-11 group， there were 1 case in CR， 12 in PR， 41 in SD，and RR, DCR were 155% and 643%. The difference of RR and DCR had no significance between both groups（P=0.834， P=0.513）. The median progressionfree survival were 4.6 and 4.1 months in CPT-11+DDP group and CPT-11 group（P=0.522）， and the median overall survival（OS） were 13.8 and 12.5 months， respectively（P=0.185）. The incidences of grade 3-4 anemia， grade 3-4 liver impairment and grade 1-4 kidney impairment were higher in CPT-11+DDP group than in CPT-11 group（P<0.05）. The incidences of grade 1-4 constipation and mucositis were lower in CPT-11/DDP group than in CPT-11group（P<0.05）. Subgroup analysis revealed that the median OS of CPT-11/DDP group was significantly better than that of CPT-11 group（15.6 months vs. 13.6 months， P=0.016）. Conclusion Compared with CPT-11monotherapy，CPT-11/DDP regimen shows no survival benefit as second-line treatment for advanced gastric cancer. However， intestinal type of gastric cancer can benefit from CPT-11/DDP regimen，and side effects are well tolerated，worthy of further observation.