It has been reported that inflammation and immune system are related to prostate cancer. The neutrophil-to-lymphocyte ratio (NLR), as well as the platelet-to-lymphocyte ratio (PLR), have already been proposed as new indices to help diagnose prostate cancer (PCa). However, the monocyte-to-lymphocyte ratio (MLR) with regard to PCa has rarely been mentioned.To investigate the capability of the MLR to predict PCa.Patients who were pathologically diagnosed with PCa in our hospital and healthy control subjects who conformed to the inclusion criteria were enrolled. Patient data were recorded, including age, complete blood counts, blood biochemistry, and serum prostate-specific antigen (PSA) levels. The differences in these data between the groups were analyzed and the diagnostic value of the MLR was compared with PSA.Our study included a total of 100 patients with PCa and 103 healthy control subjects. Patients with PCa presented with a significantly higher NLR, MLR, and PLR compared to control subjects. However, the hemoglobin and lymphocyte levels were lower (P < .05) in PCa patients. The area under the curve (AUC) of PSA and ratio of free/total serum prostate-specific antigen were 0.899 (95% confidence interval [CI]: 0.857-0.942) and 0.872 (95% CI: 0.818-0.926), respectively, while the AUC of the MLR was 0.852 (95% CI: 0.798-0.906), which was higher than that of the NLR, PLR, and any other blood parameters. Additionally, the optimal cut-off value of the MLR for PCa was 0.264, with a specificity of 87.4% and a sensitivity of 72.0%. An evaluation of the diagnostic value of MLR + PSA gave an AUC of 0.936 (95% CI: 0.902-0.970). However, the AUC of MLR + PSA + f/tPSA was 0.996 (95% CI: 0.991-1.000). The diagnostic value of MLR + NLR + PSA gave an AUC of 0.945 (95% CI: 0.913-0.977), and the specificity is 0.971.PSA remains the most important diagnostic indicator. MLR combined with PSA and f/tPSA has the higher predictive value than PSA. It suggests that MLR may be another good predictive indicator of PCa. It can help reduce the clinical false positive rate.Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.