Chronic malnutrition, abnormal blood clotting, and systemic inflammation contribute to the occurrence and progression of colon cancer. This study aimed to assess the diagnostic utility of the 100fibrinogen-to-prealbumin ratio (FPR), 100fibrinogen-to-albumin ratio (FAR), 100C-reactive protein-to-albumin ratio (CAR), and 100C-reactive protein-to-prealbumin ratio (CPR) in aiding the diagnosis of colon cancer. A total of 129 patients with colon cancer were enrolled between April 2015 and August 2022. While 129 patients with colon adenoma were selected as the control group. The serum levels of FAR, FPR, CAR, CPR, CEA, and CA125 in the colon cancer group were significantly higher than those in the colon adenoma group (P < .05). In Logistic regression analysis, high FAR and high FPR were identified as independent risk factors for colon cancer. Receiver operating characteristic (ROC) curve analysis results showed that Among the combined measures, FAR, FPR, CAR, and CPR had the highest diagnostic efficacy in distinguishing colon cancer from colon adenomas (AUC = 0.886, Sen = 80.62%, Spe = 81.40%). Thus, FAR, FPR, CAR, and CPR may serve as valuable biomarkers for the diagnosis of colon cancer, and the combined detection of FAR, FPR, CAR, and CPR can enhance the diagnostic efficiency for both colon cancer and colon adenoma.