To investigate the difference in messenger ribonucleic acid (mRNA) and protein expression of growth arrest DNA damage-inducible gene 45α (GADD45α), mouse double minute 2 homolog (MDM2), and P73 in cancer and cancer-adjacent tissues in patients with non-small-cell lung carcinoma (NSCLC).We compared the mRNA expression of GADD45α and MDM2 and the protein expression of GADD45α, MDM2, and P73 in lung cancer and cancer-adjacent tissues in NSCLC patients by quantitative real-time PCR, immunohistochemistry (IHC), and Western Blot (WB). We analyzed GADD45α, MDM2, and P73 expression in patients with different pathological types of NSCLC, and the correlation of these genes with gender, smoking history, and TNM/T stages.IHC results suggested that MDM2 protein expression significantly increased in cancer tissues in female patients (P = .01), but not in male patients. In addition, WB results indicated that P73 protein expression significantly decreased in cancer tissues in patients with adenocarcinoma (P = .03), but not squamous carcinoma.MDM2 and P73 protein levels were differentially regulated in cancer and cancer-adjacient tissues in patients with sub types of NSCLC. There was no significant difference in GADD45α expression between cancer and cancer-adjacent tissues in NSCLC patients.