To evaluate the importance of mutations of p53 and K-ras genes in the prognosis of patients with non-small cell lung cancer, one hundred and forty-four patients who underwent surgery were studied. DNA was extracted from frozen specimens. Polymerase chain reaction-single strand conformation polymorphism and sequencing were performed to investigate mutations of p53 from exon 5 to 8, and mutations of exon 1 of K-ras. Mutations of p53 gene occurred in 35. 4% of patients, and mutations of the K-ras gene in 8.3%. The overall survival rate of non-small cell lung cancer patients with wild-type K-ras was better than that of patients whose tumors had mutations of K-ras (P=0.0330). Among patients with adenocarcinoma of the lung, the overall survival rate of patients with wild-type p53 was strikingly better than that of patients whose tumors had mutations of p53 (P=0.0234). Multivariate analysis with the Cox regression model of all patients with non-small cell lung cancer and those with adenocarcinoma indicated that mutations of K-ras best correlated with the overall survival rate (P=0.0005 and P=0.0361, respectively). In conclusion, evaluation of mutations of both the p53 and K-ras genes in the lung tumors might be useful for assessing the prognosis, especially in patients with adenocarcinoma.