Neuregulin-1 (NRG1) levels were elevated in prostate cancer patients receiving androgen deprivation therapy (ADT). However, it remains unclear whether NRG1 levels could predict castration-resistant prostate cancer (CRPC) progression. Prostate cancer patients were divided into CRPC and NCRPC (non-CRPC) groups. Baseline clinicopathological characteristics and prostate-specific antigen (PSA) levels were compared among two groups. Subsequently, the levels of NRG1 in blood and tumor tissue were detected using enzyme-linked immunosorbent assay, western blotting, and qPCR. The predictive value of NRG1 was evaluated using receiver operating characteristic (ROC) analysis. Meanwhile, the correlation of NRG1 with Gleason score and PSA levels was analyzed using Spearman analysis. The comparison analysis showed that TNM classification, Gleason scores, and PSA levels were significantly correlated to CRPC. Moreover, the serum NRG1 and the protein and mRNA levels of NRG1 were higher in CRPC patients than in NCRPC patients. ROC analysis unveiled that NRG1 levels in the patients before ADT could predict CRPC progression. Moreover, Spearman analysis also showed that NRG1 was correlated to Gleason scores and PSA levels. Serum NRG1, NRG1 protein, and NRG1 mRNA in tumor tissue from prostate cancer patients before ADT could predict the incidence of CRPC in patients receiving ADT.