Despite previous reports implying a role of β2-microglobulin (β2M) in the development of prostate cancer (PCa), the correlation of serum β2M with the clinicopathological features, therapy efficacy and prognosis of patients with PCa have not been fully clarified. The present study aims to investigate the serum levels of β2M in patients with PCa and explore the potential use of β2M as a tumor marker for diagnosis, treatment and prognosis of PCa.Serum β2M levels in 120 patients with PCa, 50 patients with benign prostate hyperplasia (BPH) and 85 healthy age-matched controls were measured by enzyme immunoassay. The correlation of serum β2M with the clinicopathological features, therapy efficacy and the prognosis of PCa were subsequently assessed.Our results showed that: (i) PCa patients had significantly higher levels of β2M compared to those of patients with BPH or those of healthy controls. (ii) Serum β2M were markedly elevated in patients with high stage or grade PCa as compared to patients with low stage or grade PCa. (iii) We measured significantly higher levels of β2M in patients with metastasis as compared to patients lacking metastasis. (iv) During follow-up, serum β2M showed a marked decrease after successful therapy and a significant further increase in recurrent disease.Our results demonstrate that serum β2M is correlated closely with the clinical stage, Gleason grade, PSA, distant metastasis and therapy efficacy in patients with PCa. Serum β2M may be a useful biomarker for clinical diagnosis, follow-up and prognosis of PCa.