Objective To explore the diagnostic significance of microRNA-4286 (miR-4286) for prostate cancer through detecting its expression in patients with an elevated serum prostate-specific antigen (PSA) level. Methods We selected 171 patients with an elevated serum PSA level who underwent prostate biopsy at Day Ward between Mar. 2016 and Aug. 2016 in Changhai Hospital of Second Military Medical University; we determined and compared the expression of serum miR-4286 in 50 patients with prostate cancer and 121 with benign prostate diseases by qPCR assay. The serum miR-4286 levels were analyzed at pre-operation and three-day post-operation in 10 patients with benign prostate disease and 15 patients with prostate cancer, and at pre-operation and seven-day post-operation in 8 cases with prostate cancer. The receiver operating characteristic curve was used to evaluate the diagnostic performance of miR-4286 for prostate cancer. Results The expression of miR-4286 showed a significant difference between the prostate cancer and benign prostatic disease patients (P<0.05). The expression of 3-day post-operative miR-4286 was significantly elevated compared with pre-operation in the prostate cancer patients (P<0.05); there was no significant difference in the expression of miR-4286 between pre-and 7 days post-operation in the prostate cancer patients (P>0.05) or between pre-and 3 days post-operation in the benign prostatic disease patients (P>0.05). The areas under curve of the miR-4286 and PSA were 0.653 (cut-off value 3.72, sensitivity 68.75%, specificity 60.06%) and 0.733 (cut-off value 11.38 ng/mL, sensitivity 57.16%, specificity 92.35%), respectively. Conclusion miR-4286 has a good diagnostic value and may be a new biomarker for liquid-biopsy in prostate cancer.