Objective: The goal of this study was to determine miR-223 and miR-152 expression in serum and tissues of patients with prostate cancer (PCa) and the significance in clinical practice. Methods: Serum and tissue specimens and normal adjacent tissue specimens from 90 patients and serum from 80 healthy individuals were collected. qRT-PCR was used to detect miR-223 and miR-152 expression in serum and tissue samples. The relationship between miR-223 and miR-152 expression and clinicopathological parameters was analyzed. Results: miR-223 expression in PCa serum was significantly higher than in controls (P = 0.004, while miR-152 expression in PCa serum was significantly lower (P = 0.017). Compared to the control group, relative miR-223 expression, tumor differentiation, TNM staging, prostate specific antigen, lymph node metastasis, and Gleason score significantly differed from the PCa group (All P < 0.05). A significant correlation was observed between miR-152 relative expression and differentiation, lymph node metastasis, and Gleason score (All P < 0.05). Pearson correlation analysis showed that miR-223 and miR-152 expression in the PCa serum was positively correlated with expression in PCa tissue. Multivariate analysis showed that pathological stage, TNM staging, lymph node metastasis, and miR-223 and miR-152 expression levels were independent prognostic factors affecting the overall survival time of patients (P = 0.005 and 0.008, respectively). Conclusion: miR-223 and miR-152 expression may be involved in PCa occurrence and development and related to the degree of tumor differentiation and lymph node metastasis. These expression levels may be independent prognostic indicators for PCa.