Abstract. The p73 gene is a structural and functional homolog of the p53 gene, which has a crucial role in mediating cell cycle arrest and apoptosis. Numerous previous studies have investigated the polymorphism of p73 G4C14-to-A4T14 at exon 2, as it was suggested to affect gene expression and result in functional significance. However, the correlation of this polymorphism with clinicopathological variables of patients with non-small cell lung cancer (NSCLC) remains to be elucidated. The aim of the present study was to examine the association between the gene polymorphism of p73 G4C14-to-A4T14 and the risk of developing NSCLC. The single-nucleotide polymorphisms of p73 G4C14-to-A4T14 were genotyped using polymerase chain reaction with confronting two-pair primers and direct DNA sequencing in 186 NSCLC patients and 196 cancer-free controls. χ 2 -tests and logistic regression analysis were used to analyze the experimental data, including the determination of odds ratio (OR), 95% confidence intervals (95% CIs) and P-values. The results demonstrated that the AT/AT genotype was associated with a significantly decreased risk of NSCLC (P= 0.010; OR= 0.370; 95% CI= 0.170-0.806) compared with the GC allele genotypes including GC/GC and GC/AT. In addition, carriers of the AT allele exhibited a significantly reduced risk of NSCLC (P= 0.038; OR= 0.713; 95% CI= 0.517-0.983) compared with non-carriers. In conclusion, these results indicated that the p73 G4C14-to-A4T14 polymorphism was a potential marker of NSCLC genetic susceptibility. However, further studies with a larger population are required in order to confirm these results.