This study was designed to investigate the correlation between proto-oncogene POK erythroid myeloid ontogenetic factor (Pokemon) and oncogene, mouse double minute 2 homolog (MDM2) in the carcinogenesis of lung squamous cell carcinoma in rats. Protein and messenger ribonucleic acid (mRNA) expressions of Pokemon and MDM2 in different stages of rat lung squamous cell carcinoma were measured using immunochemistry staining and in situ hybridization assays. Lung squamous cell carcinoma was viewed under the microscope in 60 rats (success rate: 80%) after treatment with carcinogen. Among these rats, 21 had bronchial epithelial hyperplasia, 13 had atypical hyperplasia, 28 had carcinoma in situ, 20 had invasive carcinoma and 16 had metastatic carcinoma. There were significant differences in the Pokemon and MDM2 expressions between the control group and the atypical hyperplasia group or squamous cell carcinoma group (p < 0.05). There were also significant differences in both genes between the non-metastatic carcinoma group and the metastatic carcinoma group (p < 0.05). Pokemon expression was positively correlated with MDM2 expression (r = 0.616, p = 0.000). These findings indicate that Pokemon and MDM2 were highly expressed in rat lungs following carcinogenesis in lung squamous cell carcinoma. The expression of Pokemon and MDM2 may contribute to the genesis and development of lung squamous cell carcinoma in rats.