To investigate the 4- hydroxynonenal (4-HNE) expression and its role in androgen antagonism of prostate cancer. Methods Immunohistochemistry was used to detect the expression of 4-HNE of 40 cases of prostate cancer and 42 cases of benign prostatic hyperplasia, and the relationship between 4-HNE expression of tumor progression was analyzed. Results The expression of 4-HNE in 42 cases of benign prostatic hyperplasia was low, only 4.8%. 4-HNE in prostate hyperplasia showed high level. By positive expression of ratings analysis, positive rate of castration-resistant prostate cancer was significantly higher than non-castration-resistant prostate cancer, the difference was statistically significant (P <0.01). Conclusion The expression of 4-HNE may play an important role in androgen antagonism and the progression of prostate cancer.