Abstract: Objective To explore the clinical efficacy of raltitrexed combined with oxaliplatin in the treatment of patients with advanced colorectal cancer (CRC) and its influence on tumor necrosis factor-α (TNF-α) and interleukin-2 (IL-2).Methods A total of 69 patients with advanced CRC were selected and randomly divided into treatment group (n =35) and control group (n =34).Treatment group was treated with raltitrexed combined with oxaliplatin,while control group was treated with capecitabine combined with oxaliplatin.Short-and long-term clinical efficacy as well as the changes of levels of TNF-α and IL-2 before and 3 weeks after treatment were compared,and the occurrence rates of toxic and adverse reactions were recorded during treatment.Results Treatment group was slightly higher than control group in clinical efficacy and disease control rate (P ＞0.05),and there was also no significant difference between two groups in time to progression (TFP)and median overall survival time (OS) (P ＞ 0.05).After treatment for 3 weeks,levels of TNF-α and IL-2 increased in both groups (P ＜ 0.01),which increased more significantly in treatment group than control group (P ＜ 0.01).Treatment group was significantly lower in the rates of diarrhea,nausea and vomiting,and neutropenia,bur was prominently higher in the increase of transaminase than control group (P ＜ 0.05).Conclusion Rahitrexed combined with oxaliplatin has similar clinical efficacy to capecitabine combined with oxaliplatin in the treatment of advanced CRC,but the former is mild in toxic and adverse reactions.