Objective: Although 5-fluarouracil-based chemotherapy has become a standard regimen for treatment of advanced colorectal cancer, the efficacy, as second line therapy, is not high. It is necessary to find a new regimen as a substitute for these patients. The study was to evaluate the short-time effects and toxicity of combination of HCPT plus L-OHP regimen in treatment of advanced colorectal cancer. Methods: Forty-seven patients with pathological evidence of advanced colorectal cancer were enrolled and were treated with HCPT plus L-OHP regimen for 86 cycles. All patients were treated with L-OHP 130mg/m2 day 1 and HCPT 6 mg/m2 day 1-4, the chemotherapy was repeated every 3 weeks as a cycle. The Short-time efficats and side effects were evaluated after 2 cycles for each patient. Results: 38 cases can be evaluated to short-time effects and achieved the overall response rate (CR+PR) was 36.8%. KPS improved in 20 cases (52.6%). In the total 86 cycles, the leucopenia occurred in 59 cycles (68.6%),18 cycles (30.5%)in grade Ⅲ and Ⅳ and the diarrhea occurred in 48 cycles (55.8%), 18cycles (37.5%) in grade Ⅲ and Ⅳ. Conclusion: A satisfied response rate was obtained in advanced colorectal cancer patients treated by HCPT plus L-OHP regimen, especially who were the failure of first-line chemotherapy with 5-FU. The limited-dose toxicity was leucopenia and diarrhea.