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Background: Inflammation has a prominent role in cancer development and interleukin (IL)-33 has both inflammatory and anti-inflammatory properties. The aim of this study was to measure IL-33 quantities and genetic alterations in the rs1929992 SNP within IL-33 gene in patients with prostate cancer (PC). Methods: This investigation was conducted on blood specimens from 150 newly diagnosed PC patients and 150 healthy age-matched controls. Serum IL-33 measurements and genotyping were performed by ELISA and PCR-RFLP, respectively. Results: Elevated IL-33 quantities were detected in PC patients compared with controls (P < 0.001). The PC patients with Gleason scores 7-10 displayed greater IL-33 quantities than those who had Gleason scores 1-6 (P < 0.001). Significant differences were found between PC stages regarding the IL-33 serum levels (P < 0.001). The frequencies of the genotype GG and allele G in rs1929992 SNP were higher, whereas the frequencies of the genotype AA and allele A were lower in PC patients, as compared with controls (P < 0.05, 0.01, P < 0.002 and P < 0.01, respectively). The genotype GG and allele G of rs1929992 SNP were associated with a greater risk of cancer development (OR: 4.533; P < 0.001, and OR: 1.516; P < 0.01, respectively). The IL-33 levels were not significantly different between the subjects carrier genotypes AA, AG and GG, or alleles A and G in rs1929992 SNP, neither in patients nor in controls. Conclusion: Higher IL-33 quantities were found in patients with PC, especially in those with greater stages which raises the possiblity that IL-33 may contribute to PC progression. The rs1929992 SNP-related genotype GG and allele G were associated with an increased risk of cancer development.