Objective To investigate the expression level of guanylate-binding protein 1/2 (GBP1/2) in patients with colorectal cancer (CRC) and its relationship with prognosis.Methods The CRC tissues and paracancerous tissues of 86 CRC patients admitted to our hospital between June 2016 and June 2019 were gathered for research. Quantitative real-time PCR (qRT-PCR) method/immunohistochemistry method were applied to detect the mRNA/protein expression levels of GBP1 and GBP2. The relationship between the expression levels of GBP1 and GBP2 in CRC tissues and the clinicopathological characteristics was analyzed. Kaplan-Meier survival curve and log-rank test were used to analyze the relationship between the expression levels of GBP1 and GBP2 in CRC tissues and the prognosis. The factors affecting the prognosis of CRC patients were analyzed by COX regression.Results Compared with the paracancerous tissues, the mRNA expression levels of GBP1 and GBP2 and the rates of positive expression of GBP1 and GBP2 proteins in CRC tissues were decreased (P<0.05). The rates of positive expression of GBP1 and GBP2 proteins in poorly differentiated CRC tissues were lower than those in moderately and well differentiated CRC tissues (P<0.05). The rates of positive expression of GBP1 and GBP2 proteins in stage Ⅲ CRC patients were lower than those in stage Ⅰ~Ⅱ CRC patients (P<0.05). The cumulative survival rates of CRC patients in GBP1 and GBP2 positive groups were higher than those in GBP1 and GBP2 negative groups (P<0.05). GBP1 and GBP2 were independent protective factors affecting the prognosis of CRC patients (P<0.05), and TNM stage were the independent risk factor (P<0.05).Conclusion The GBP1 and GBP2 were lowly expressed in CRC tissues, and both were related to the prognosis of CRC patients. GBP1 and GBP2 may be potential indicators for evaluating the prognosis of CRC patients.