Suppressors of cytokine signaling (SOCS) proteins have been identified as negative feedback regulators of cytokine-mediated signaling in various tissues, and demonstrated to play critical roles in tumorigenesis and tumor development of different cancers. The involvement of SOCSs in human prostate cancer (PCa) has not been fully elucidated. Thus, the aim of this study is to investigate the expression patterns and the clinical significance of SOCSs in PCa. The expression changes of SOCSs at mRNA and protein levels in human PCa tissues compared with adjacent benign prostate tissues were, respectively, detected by using real-time quantitative reverse transcriptase-polymerase chain reaction (QRT-PCR) and immunohistochemistry analyses. The associations of SOCSs expression with clinicopathological features and clinical outcome of PCa patients were further statistically analyzed. Among SOCSs, both QRT-PCR and immunohistochemistry analyses found that SOCS2 expression was upregulated (at mRNA level: change ratio = 1.98, P = 0.031; at protein level: 5.12 ± 0.60 vs. 2.68 ± 0.37, P = 0.016) and SOCS6 expression was downregulated (at mRNA level: change ratio = -1.65, P = 0.008; at protein level: 3.03 ± 0.32 vs. 4.0.72 ± 0.39, P = 0.004) in PCa tissues compared with those in non-cancerous prostate tissues. In addition, the upregulation of SOCS2 in PCa tissues was correlated with the lower Gleason score (P < 0.001), the absence of metastasis (P < 0.001) and the negative PSA failure (P = 0.009); the downregulation of SOCS6 tended to be found in PCa tissues with the higher Gleason score (P = 0.016), the advanced pathological stage (P = 0.007), the positive metastasis (P = 0.020), and the positive PSA failure (P = 0.032). Furthermore, both univariate and multivariate analyses showed that the downregulation of SOCS2 was an independent predictor of shorter biochemical recurrence-free survival. Our data offer the convincing evidence for the first time that the dysregulation of SOCS2 and SOCS6 may be associated with the aggressive progression of PCa. SOCS2 may be potential markers for prognosis in PCa patients.