The purpose of the present study was to determine the relationship between interleukin-18 (IL-18) -607 A/C polymorphism and the risk of non-small-cell lung cancer (NSCLC) and its impact on the serum IL-18 level. The genotyping of IL-18 -607 A/C polymorphism was detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The results showed that the AA/AC genotype distribution in NSCLC patients was significantly higher than that of healthy controls (P=0.02). However, no significant differences were found between the two subgroups when stratified by clinical characteristics. Furthermore, serum IL-18 levels were found to be significantly higher in the NSCLC patients than in the controls (P=0.01) as detected by enzyme-linked immunosorbent assay analysis. There was no correlation between serum IL-18 levels and different genotypes. In conclusion, these findings suggest that IL-18 -607 A/C polymorphism increases the risk of NSCLC in the Chinese population, and this polymorphism could not functionally affect the IL-18 levels.