Objective: To investigate the relationship between the level of thioredoxin reductase (TrxR) and the short-term efficacy and progression-free survival (PFS) of advanced colorectal cancer, and explore the potential value of TrxR on the efficacy evaluation and disease control in advanced colorectal cancer. Methods: A total of 108 patients with advanced colorectal cancer were included. The level of TrxR in the peripheral blood of the patients was detected. After 2 cycles of chemotherapy, the level of TrxR in the peripheral blood was detected again. Response Evaluation Criteria in Solid Tumors (1.1 version) was used to evaluate the treatment effect. The TrxR value fluctuated before and after treatment. So, the relationship between the fluctuation and the treatment efficacy was explored. The mean value of TrxR before treatment was 8.6856 U/mL. This value was used as the cutoff value to divide the enrolled cases into high expression group and low expression group. Kaplan-Meier method and COX regression were used to explore the correlation between TrxR expression level and PFS. Results: After two cycles of chemotherapy, the TrxR level of patients with partial response decreased after treatment compared with before treatment, and the difference was statistically significant (P=0.001). Kaplan-Meier analysis showed that patients with low TrxR expression before treatment had longer PFS than those with high TrxR expression before treatment, and the difference was statistically significant (P=0.023). COX univariate analysis showed that TrxR expression level before treatment was an independent risk factor for the progression of advanced colorectal cancer (P=0.019). COX multivariate analysis also suggested the same result (P=0.022). Conclusion: There is a close relationship between the expression level of TrxR and the short-term efficacy and disease progression of patients with advanced colorectal cancer.