Objective: To investigate the clinical significance of using serum prostate-specific antigen (PSA) for prostate cancer screening. Methods: In 4,848 men aged 50 years or older, serum PSA was detected in 33 cases of prostate cancer (screening group), compared with 28 patients with prostate cancer (clinical group) treated in the same period. Results: There were 461 patients with positive PSA (PSA≥4ng/ml) in the screening population, and the detection rate was 9. 5%, among which 33 cases of prostate cancer were confirmed, accounting for 6. 8‰ of the screened patients. The age of the screening group was (73.2±8.0) years, and the difference was not significant compared with the clinical group; the percentage of PSA ≥20 ng/ml was 42.4% in the screening group and 71.5% in the clinical group, and the difference was significant compared with the two groups; the percentage of (A+B) stage in the screening group was 69.7% and the percentage of (A+B) stage in the clinical group was 35.7%, P<0.01; the percentage of radical prostatectomy in the screening group was 16 (48). In the screening group, 16 cases (48.5%) underwent radical prostatectomy, and 6 cases (21.4%) in the clinical group. Conclusion: The use of serum PSA screening can diagnose prostate cancer at an early stage and provide patients with better treatment opportunities.