The prolyl hydroxylase domain enzymes (PHDs) play the most notable role in cellular oxygen sensing and oxygen homeostasis, the transcription of PHD genes are involved in the protection against hypoxia and oxidative stress. Intratumoral hypoxia exists in malignant solid tumors primarily due to rapid cancer cell proliferation with high metabolic demands and defective structural and functional vasculature. Previous studies have demonstrated that all the three PHDs have the ability to hydroxylate hypoxia inducible factor (HIF) polypeptides, which are the key molecules in maintaining the oxygen homeostasis. However, PHDs play multiple physiological and pathological roles. There is scant data regarding expression of PHDs genes in non-small cell lung cancer (NSCLC) tissues. In Addition, the relationship between PHDs and apoptosis has never been explored in NSCLC. In this article, we examined the expression of PHD genes and their relationship with the tumor behavior and apoptosis-associated factors in NSCLC. Our results indicated that the expression of PHDs was much higher in lung cancer tissue than that of adjacent normal tissue, and the high expression of PHD3 was associated with early tumor stage and well differentiation in NSCLC. Moreover, increased PHD3 expression was significantly correlated with the low expression of Bcl-2, suggesting its potential role in inducing apoptosis.