Abstract: Objective:To investigate the efficacy and toxicity of oxaliplatin reintroduction combined with raltitrexed as second-line che -motherapy after the first-line oxaliplatin based chemotherapy in advanced colorectal cancer patients. Methods:The 48evaluable pa-tients with advanced colorectal cancer following disease progression prior to the first-line chemotherapy were treated with oxaliplatin and raltitrexed (raltitrexed 3 mg/m2 ivgtt d 1, oxaliplatin 100 - 130 mg/m2 ivgtt d 1, q21d). All 48patients were divided into two groups: Group A, non-oxaliplatin-based regimens as the first-line chemotherapy, 20cases; Group B, oxaliplatin-based regimens as the first-line chemotherapy,28cases. Each group was evaluated every two cycles. Results:The response rates (RR) of Groups A and B were 30. 0% (6/20) and 32. 1% (9/28), the disease control rates (DCR) were 80. 0% (16/20) and 75. 0% (21/28), the median progression free survival time (mPFS) was 6. 5 and 7. 0 months, and the median overall survival time (mOS) was 10and 13months, respectively. No statistical sig-nificance was observed between the two groups in their RR, CR, mPFS, and mOS (P=0. 264 , 0. 514 , 0. 713 , 0. 788 ), respectively. The most common adverse effects observed were Ⅰ- Ⅱgrades of bone marrow suppression, aminotransferase abnormality, and digestive toxici -ties. The incidence of neurotoxicity (Ⅰ- Ⅱgrades) between the two groups was similar. Conclusion: Instead of irinotecan combined with raltitrexed, oxaliplatin reintroduction combined with raltitrexed for second-line chemotherapy after the first-line oxaliplatin-based chemotherapy in advanced colorectal cancer patients is feasible.