Abnormalities of p53 gene can lead to the production of p53 antibodies (p53-Abs) in the serum of cancer patients. This study was designed to investigate the prevalence of p53-Abs in 133 lung cancer patients and the distribution of these antibodies to clinicopathologic features and smoking status. Twenty five (18.8%) lung cancer patients were found to have p53-Abs. The presence of p53-Abs did not correlate with sex or age but showed frequent association with tumors of squamous cell carcinoma (31%) in comparison with adenocarcinoma (13.6%) (P=0.052). There was a statistically significant difference in the incidence of p53-Abs between early disease group (stage I-II) and the advanced group (stage III-IV) (P=0.036), however, there was no relationship between the presence of p53-Abs and overall survival. Interestingly, the frequent of p53-Abs was higher in smokers (27.1%) than in non-smokers (13.6%), though the difference was of borderline of statistical significance (P=0.061). These findings suggested that p53-Abs could be a potential biomarker for the study of individual with lung cancer.