The identification of suitable biomarkers holds significant clinical importance for the early detection of benign prostatic hyperplasia (BPH) and prostate cancer (PCa). This study aimed to conduct a comprehensive analysis of the relationship between BPH and blood and urine biomarkers (BUB), as well as PCa and BUB. Candidate single nucleotide polymorphisms associated with BPH or PCa were derived from recent genome-wide association studies. The UK Biobank cohort comprised 363,228 individuals with BUB test data, enabling the calculation of a polygenic risk score for BPH or PCa. Bidirectional 2-sample Mendelian randomization was employed to assess the potential causal association between candidate BUB and BPH, as well as between BUB and PCa. In this study, a notable correlation was observed between BPH and gamma-glutamyl transferase (r = 1.061658447, P = .028697428). PCa exhibited significant associations with insulin-like growth factor 1 (r = 1.119051258, P = .004101067), Lipoprotein A (r = 1.120348291, P = .038093372), total protein (r = 0.87643517, P = .01657563), and non-albumin protein (r = 0.905333153, P = .03103913). The findings offer valuable insights into the significance of BUB in the timely identification and management of BPH and PCa.