<p>Per- and polyfluoroalkyl substances (PFAS), as endocrine disruptors, may increase the risk of prostate cancer by interfering with the endocrine system, however, current population-based evidence is still limited, and there are relative few types of PFAS involved. This study aims to investigate the association between exposure to 18 kinds of PFAS and the incidence of prostate cancer in southwest China. In the case–control study, plasma samples from 97 PCa patients and 111 controls without a family history were analyzed using UPLC-MS/MS. The association between PFAS concentrations and prostate cancer was analyzed using Mann–Whitney <i>U</i> tests and Bayesian logistic regression. The detection limits of the proposed UPLC-MS/MS method ranged from 0.00070 to 0.30&#xa0;ng/mL. The detection rate of most PFAS is greater than 75%, except for Perfluorodecanesulfonic acid (PFDS), Perfluorohexanoic acid (PFHxA), Perfluorohexadecanoic acid (PFHxDA), Perfluorooctadecanoic acid (PFODA), Perfluoropentanoic acid (PFPeA), Perfluorotetradecanoic acid (PFTeDA). Mann–Whitney <i>U</i> test results showed that differences in Perfluorobutanoic acid (PFBA), Perfluorohexanesulfonic acid (PFHxS), Perfluoroheptanesulfonic acid (PFHpS), Perfluorooctanesulfonic acid (PFOS), and Perfluoroundecanoic acid (PFUnDA) between the two groups were statistically significant, suggesting that exposure to these compounds may be associated with prostate cancer occurrence. Bayesian analysis showed no significant correlation for several PFAS, but Perfluorooctanoic acid (PFOA) [OR²_≥4.02 = 2.86, 95% CI² (1.64, 6.28)], Perfluorononanoic acid (PFNA) [OR²_≥1.61 = 3.82, 95% CI² (1.22, 16.08)], and PFUnDA [OR²_≥0.462 = 7.14, 95% CI² (1.12, 68.7)] demonstrated a positive correlation in high-concentration groups. Conversely, PFOS showed a negative correlation after adjustment [OR²_≥3.71 = 0.97, 95% CI² (0.87, 0.99)]. These results suggest a potential link between PFAS exposure and prostate cancer in the Chinese population, warranting further research.</p>