Abstract: Objective To analyze the efficacy and toxicities of the thalidomide-based chemotherapy on advanced colorectal cancer. Methods A total of 45 patients pathologically confirmed with advanced colorectal cancer were randomly assigned to the treatment and control group.The treatment group (22 patients) was thalidomide combined with capecitabine plus oxaliplatin regimen and control group (23 patients) capecitabine plus oxaliplatin alone. The regimens were administered for more than 2 cycles (every 3 weeks) The research endpoints were progression-free survival(PFS),objective response rate(ORR) as well as disease control rate (DCR).Drug safety and quality of life were also assessed. Results The DCR of the treatment group was higher than that of control group (68.2% vs. 43.5%,P＜0.05). The PFS and The ORR as well as the quality of life between 2 groups had no significant difference (P＞0.05). Conclusion The thalidomide-based chemotherapy on advanced colorectal cancer was well-tolerated and significantly improved the DCR, but PFS and ORR. It is worthy of further research in clinical practice.