Background & aim: Vulvovaginal Candidiasis (VVC) is a common disease affecting more than 75% of all women at least once in their lifetime. Various factors, including genetic and immunology factors, plays an important role in this disease. IL-18 is an important cytokine in immune system and has several polymorphisms in the promoter region. This study attempted to evaluate associations between IL-18 gene polymorphisms in patients with acute Vulvovaginal Candidiasis. Methods: In the present case-control study, a total of 100 women with Vulvovaginal Candidiasis and 100 healthy women in Iran were examined. DNA was extracted by saluting out method and Single nucleotide Polymorphisms of the IL-18 gene at positions -607 (C/A) and -137 (G/C) were analyzed by the Allele-specific PCR method and data were compared in both groups by using Pearson’s chi-square test and to investigate that the genotypes study in the position followed the Hardy-Weinberg equilibrium, was assessed by the Arlequin 3.1. Results: The results of this study showed that the frequency of genotypes of polymorphic position -607 C / A IL-18 genes were not significantly different in patients with vaginal Candidiasis and the control group P> 0.05. On the other hand, in patients ,there was  an association  with a significant increase in the C allele and CC genotype, of the single nucleotide polymorphisms (SNPs) at position-137G/C in the IL-18 gene promoter and Vulvovaginal Candidiasis ( P< 0.05 ) . Conclusion: Due to the fact that an increase in the expression of CC genotype and allele C, can lead to reduction of Interleukin-18 gene promoter activity and according to the impact of that activity of this cytokine can lead to Th1 system, it seems that the promoter activity of this gene may lead to reduced activity of the immune system and as a result be prone to vaginal Candidiasis