p73, a structural and functional homolog of p53, plays an important role in tumor carcinogenesis. Previous studies have suggested that the association between the p73 G4C14-to-A4T14 polymorphism and the risk of lung cancer, but the results have not been entirely consistent. We examined whether the p73 G4C14-to-A4T14 polymorphism was related to the risk of developing lung cancer in a Chinese population. The p73 G4C14-to-A4T14 polymorphism was genotyped in 293 lung cancer patients and 380 cancer-free controls of Han nationality in North China using PCR-RFLP. Multivariate logistic regression analysis was used to calculate adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs). We observed that compared with the GC/GC genotype, the genotypes containing AT allele (GC/AT + AT/AT genotypes) were associated with significantly increased susceptibility to lung cancer (OR, 1.48; 95% CI, 1.08–2.02; P = 0.014). In addition, compared with the GC/GC genotype, the GC/AT genotype was also significantly associated with increased susceptibility to lung cancer (OR, 1.46; 95% CI, 1.06–2.02; P = 0.046). Our findings suggest that the p73 G4C14-to-A4T14 polymorphism contributes to the risk of developing lung cancer in Chinese population. © 2012 Wiley Periodicals, Inc.