The association between a single-nucleotide polymorphism (SNP; -607A/C) in the promoter region of the IL-18 gene with IL-18 promoter transcription activity and the level of IL-18 protein production has been observed repeatedly. However, the association between the IL-18-607A/C (rs1946518) promoter polymorphism and IgA nephropathy (IgAN) in a Chinese Han population is still unclear. A total of 166 patients with renal biopsy-proven IgAN and 198 healthy controls were recruited for this study. The SNP was genotyped by the polymerase chain reaction and the high-resolution melting method. Clinical characteristics and pathology grading of patients with IgAN were recorded at the time of the kidney biopsy. There was a significant difference in the distribution between the AA genotype and the AC/CC genotype [P=0.007, OR (95% CI)=1.885 (1.183-3.003)]. However, no significant differences were observed between the rs1946518 SNP and quantitative traits (all P>0.05) or different pathology grades (Lee’s grading system and tubular atrophy/interstitial fibrosis according to the Oxford classification) (P=0.769 and P=0.7) of the patients. We first demonstrated that the AA genotype of the IL-18-607A/C was associated with an increased susceptibility to IgAN in this population.