Background: It has been rarely reported whether F-18-fluorodeoxyglucose ( F-18-FDG) uptake in colorectal cancer cells is associated with the expression of PD-L1. We performed a clinical pathology study to evaluate PD-L1 expression in patients undergoing surgical resection of colorectal cancer with preoperative F-18-FDG PET/CT imaging, with the aim of predicting the response of CRC patients to immune checkpoint inhibitors. Material and Methods: A retrospective analysis of patients with CRC who underwent FDG-PET imaging before surgery was performed to measure the parameters of FDG-PET imaging: the maximum standardized uptake value (SUVmax), the metabolic tumor volume (MTV), and the total lesion glycolysis (TLG) were evaluated to determine whether each parameter was associated with clinical pathology. Tumor specimens were subjected to PD-L1 staining by immunohistochemistry. Analysis of whether there is a correlation between PD-L1 expression and F-18-FDG uptake parameters in CRC. Results: PD-L1 expression level was significantly correlated with SUVmax, MTV3.0 and TLG3.0. Multivariate analysis showed that PD-L1 and TLG3.0 were independent predictors of poor DFS in patients with CRC (P=0.009; P=0.016), PD-L1 expression is closely related to the patient's lesion (TLG3.0) (P<0.01). Conclusion: The results of this study indicate that there was a significant correlation between PD-L1 expression and TLG3.0 which suggested that FDG-PET could serve as a noninvasive tool to assess the tumor microenvironment and as a predictor of PD-L1 inhibitor activity to determine the optimal therapeutic strategy for CRC. High PD-L1 expression levels and high TLG3.0 are independent risk factors for DFS differences in CRC patients.