The aim of this study was to determine whether the neutrophil-to-lymphocyte ratio (NLR), a measure of the systemic inflammatory response is associated with the overall prostate cancer detection rate in men who underwent contemporary multi (≥12)-core transrectal ultrasound (TRUS) biopsy. We reviewed the records of 3913 patients with initial prostate-specific antigen (PSA) levels ranging from 4 to 10 ng ml−1 who underwent TRUS-guided prostate biopsy between April 2006 and May 2014. NLR was calculated by prebiopsy neutrophil and lymphocyte counts. We excluded patients who had evidence of acute prostatitis, a history of prostate surgery, and any systemic inflammatory disease. A multivariate logistic regression model was used to analyze prostate cancer detection. After adjusting for confounding factors, predictive values were determined according to the receiver operating characteristic-derived area under the curve, both including and excluding the NLR variable. In univariate analyses, NLR was a significant predictor of prostate cancer detection (P < 0.001). In multivariate analyses, a higher NLR was significantly associated with prostate cancer detection after adjusting for other factors (OR = 1.372, P = 0.038). The addition of NLR increased the accuracy from 0.712 to 0.725 (P = 0.005) in the multivariate model for prostate cancer detection. NLR may be a potentially useful clinical marker in the detection of prostate cancer among men with a PSA level in the 4–10 ng ml−1 range. These findings are derived from a retrospective analysis and should be validated in larger populations through prospective studies.