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Prostate cancer (PCa) is a multifactorial disease influenced by genetic, environmental, and immunological factors. Genetic polymorphisms in the <i>interleukin-10</i> (<i>IL-10</i>) gene have been implicated in PCa susceptibility, development, and progression. This study aims to assess the contributions of three <i>IL-10</i> promoter single nucleotide polymorphisms (SNPs), A-1082G (rs1800896), T-819C (rs3021097), and A-592C (rs1800872), to the risk of PCa in Taiwan. The three <i>IL-10</i> genotypes were determined using PCR-RFLP methodology and were evaluated for their contributions to PCa risk among 218 PCa patients and 436 non-PCa controls. None of the three <i>IL-10</i> SNPs were significantly associated with the risks of PCa (<i>p</i> all > 0.05) in the overall analyses. However, the GG at rs1800896 combined with smoking behavior was found to significantly increase the risk of PCa by 3.90-fold (95% confidence interval [95% CI] = 1.28–11.89, <i>p</i> = 0.0231). In addition, the rs1800896 AG and GGs were found to be correlated with the late stages of PCa (odds ratio [OR] = 1.90 and 6.42, 95% CI = 1.05–3.45 and 2.30–17.89, <i>p</i> = 0.0452 and 0.0003, respectively). The <i>IL-10</i> promoter SNP, A-1082G (rs1800896), might be a risk factor for PCa development among smokers and those at late stages of the disease. These findings should be validated in larger and more diverse populations.