OBJECTIVE： To observe clinical efficacy and safety of irinotecan combined with tegafur， raltitrexed or 5-fluorouracil for advanced gastric cancer. METHODS： One hundred advanced gastric cancer patients with first-line regimen failure were selected as research objects from our hospital during May 2013-May 2016. According to random number table， they were divided into observation group （n＝32）， control group A （n＝33） and control group B （n＝35）. Observation group was given Irinotecan hydrochroride injection 180 mg/m2，ivgtt（d1）+Tegafur capsule 60 mg/m2，po， bid （after meal）， 2 weeks as a cycle. Control group A was given Irinotecan hydrochroride injection 180 mg/m2，ivgtt（d1）+ Raltitrexed for injection 3 mg/m2，ivgtt（d1，15 min）， 3 weeks as a cycle. Control group B was given Irinotecan hydrochroride injection 180 mg/m2，ivgtt（d1）+Calcium folinate injection 200 mg/m2，ivgtt（d1）+5-fluorouracil injection 400 mg/m2，iv+2 400～3 000 mg/m2， ivgtt（46 h），d1， 2 weeks as a cycle. On the 7th day after 2 courses of treatment， clinical efficacies of observation group and control group A were evaluated； on the 12th day after 3 courses of treatment， clinical efficacies of control group B were evaluated. Clinical efficacy and the occurrence of ADR were observed in 3 groups. RESULTS： One patient withdrew from control group A and 2 from control group B. 97 patients were included in the study finally， including 32 cases in observation group， 32 cases in control group A， 33 cases in control group B. The total remission rate of observation group （53.13％） was significantly higher than that of control group A （43.75％）and control group B （36.36％）； total control rate of observation group （81.25％） was significantly higher than that of control group A （68.75％） and control group B （57.58％）， with statistical significance （P＜0.05）.  There was no statistical significance in the incidence of ADR among 3 groups （P＞0.05）. CONCLUSIONS： Clinical efficacy of irinotecan combined with tegafur is better than irinotecan combined with raltitrexed or 5-fluorouracil in the treatment of advanced gastric cancer with good safety.