Objective To investigate the intraoperative intraperitoneal chemotherapy security with raltitrexed in advanced colorectal cancer surgical operation.Methods Sixty patients with colorectal cancer undergone surgery were randomly divided into trial group (n =30) and control group (n =30) according to the random number table method.The trial group was given surgical operation plus with intraperitoneal chemotherapy with raltitrexed.The control group was given surgical operation plus with intraperitoneal saline perfusion.Theroutine blood test,liver and kidney functions,toxic side effects and complications in two groups before and after surgery were investigated.Results The white blood cells in trial group before and after surgery was (6.36 ± 2.63) × 109/L vs.(8.20 ± 2.08) × 109/L,with statistically significant difference (t =3.06,P ＜0.05).The ratio of absolute neutrophil count in trial group before and after surgery was 65.17％ ± 10.36％ vs.72.21％ ± 10.53％ (t =3.22,P ＜ 0.05).The platelets in trial group before and after surgery was (261.03 ±84.74) × 109/L vs.(228.47 ± 58.69) × 109/L (t =2.07,P ＜ 0.05).The white blood cells,the ratio of absolute neutrophil count and the platelets after surgery had no statistically significant differeuces between the two groups (P ＞0.05).The trial group had higher 1,2 level vomiting (60.00％ vs.23.33％;x2 =8.30,P ＜ 0.05),and nausea (30.00％ vs.6.67％;x2 =5.46,P ＜ 0.05) incidence rates,but there was no statistically significant difference in other toxic side effects (P ＞ 0.05).The major complications post operation included intestinal obstruction,incision infection,abdominal cavity bleeding,and anastomotic fistula.There were equivalent complications in two groups (6.67％ vs.3.33％,x2 =0.35,P ＞0.05;10.00％ vs.6.67％,x2 =0.22,P＞0.05;0 vs.0;3.33％ vs.0,P＞0.05).Conclusion For patients with advanced colorectal cancer,intraoperative intraperitoneal chemotherapy with raltitrexed is safe and feasible,and the adverse reactions can be tolerated without increasing postoperative complications.