To investigate the value of radiomics features extracted from pre-treatment 18F-FDG PET/CT in predicting the outcomes of stage III-IV colorectal cancer (CRC), which may assist in clinical management strategies and precise treatment of stage III-IV CRC.124 patients with pathologically confirmed stage III-IV CRC who underwent pre-treatment 18F-FDG PET/CT scans were enrolled in this study. The least absolute shrinkage and selection operator Cox regression (LASSO-Cox) was used to select radiomics features, and the radiomics scores (Rad-scores) were calculated to build radiomics models. The performance of radiomics models was represented by the concordance index (C-index) and compared with clinical models and complex model. The bootstrap resampling method was used to create validation sets. Additionally, nomograms were developed based on complex models.The C-indices of the radiomics model for predicting PFS and OS were 0.712 (95%CI: 0.680-0.744) and 0.758 (0.728-0.789), respectively. In the clinical model, these values were 0.690 (0.664-0.0.717) and 0.738 (0.709-0.767), respectively. However, in the complex model were 0.734 (0.705-0.762) and 0.780 (0.754-0.807), respectively. The Kaplan-Meier curves demonstrated that the radiomics model could effectively separate patients with stage III-IV stage CRC into high- and low-risk groups (p < 0.001). Multivariate Cox regression analysis confirmed the independent prognostic value of Rad-scores.Pre-treatment 18F-FDG PET/CT radiomics features can stratify the risk of patients with stage III-IV CRC and accurately predict their outcomes. These findings could be clinically valuable for precision treatment and management decisions in stage III-IV CRC.© 2023 The Authors.