Globally, lung cancer is one of the most prevalent and deadly cancers. Exposure to environmental risk factors and genetic susceptibility are also associated with the incidence of the disease. Patients may produce p53 antibodies (p53-Abs) in their serum as a result of p53 gene abnormalities. Aim: The study aimed to investigate the utility of detecting serum biomarker such as p53-Abs, carcinoembryonic antigen (CEA), and some other abnormalities characterizing patients with NSCLC. Methods: A total of 124 patients with NSCLC and 100 apparently healthy controls were evaluated for measuring serum p53-Abs and CEA levels by ELISA. Results: NSCLC patients presented with specific characteristics. The histological assessments were classified as (79.9%) LUAD, (8.9%) LUSC, LCC (6.4%) and (4.8%) other histological cell types with histological grades divided as grade I (1.7%), grade II (34.2%) and grade III (64.2%). The immuohistochemical analysis revealed that (51.6%) of patients were positive for TTF1, (70.2%) positive for CK7 and (33.6%) positive for napsin. Patients were also had significant elevated levels of p53-Ab, and CEA, compared to the controls (p<0.05). Conclusions: Detection of serum p53-Abs and CEA levels are important tumor markers characterizing NSCLC. P53 can be served as possible biomarker for the occurrence of p53 gene mutation in NSCLC patients.