Background The prognosis of patients with prostate cancer (PCa) remains poor. Methods GSE16560, GSE32448, GSE79957, GSE17951, and TCGA‐PRAD were reanalyzed to evaluate the expression of homeobox B7 (HOXB7) between PCa tissues and normal prostate tissues and to characterize the correlation between the expression of HOXB7 and the clinicopathological features of patients with PCa. Gene set enrichment analysis was conducted to investigate the mechanisms. Results HOXB7 was upregulated in PCa tissues (P = 0.0005). Both the univariate and multivariate analyses demonstrated that the expression of HOXB7 was correlated with the Gleason score and TNM staging of patients with PCa. The Gleason score and TNM staging were higher in the HOXB7 high expression group. The overall survival (hazard ratio [HR] = 0.632; 95% confidence interval [CI]: 0.4773‐0.8369; P = 0.0014) and progression‐free survival (HR = 0.544; 95% CI: 0.3157‐0.9373; P = 0.0283) favored patients with PCa in HOXB7 low expression group over those in HOXB7 high expression group. PCa samples in HOXB7 low expression group were enriched in gene sets associated with the epithelial mesenchymal transition, apical junction, angiogenesis, ultraviolet response, and hypoxia. Conclusions HOXB7 might be an independent prognostic factor of patients with PCa.