It has been demonstrated that estrogens are able to enhance lung tumorigenesis by estrogen receptor (ER) pathway. ER signaling is a highly complex process that requires a number of different coactivators, including proline-, glutamic acid- and leucine-rich protein-1 (PELP1). We studied PELP1 transcript and protein levels in cancerous and histopathologically unchanged lung tissues obtained from 73 patients diagnosed with non-small cell lung cancer (NSCLC). We observed increased levels of PELP1 transcript (P=0.00001) and protein (P=0.00001) in tumor tissues compared to adjacent histopathologically unchanged tissues. Significant increase of PELP1 transcript/protein level was found in all patients, regardless of gender (males: P=0.0003/P=0.000003; females: P=0.0005/P=0.02), age (≤ 60 patients: P=0.042/P=0.016; >60 patients: P=0.00001/P=0.00001) or histopathological type of tumor (adenocarcinoma [ADC]: P=0.004/P=0.0006; squamous cell carcinoma [SSC]: P=0.0009/P=0.0008). Increased PELP1 transcript/protein levels were also correlated with some lung cancer stage (1a: P=0.07/P=0.02; 1b: P=0.001/P=0.03; 2a: P=0.012/P=0.001), tumor size (T2a: P=0.0006/P=0.001) and lymph node metastasis (N0: P=0.0003/P=0.0006; N1: P=0.017/P=0.003). Moreover, significant increase in PELP1 transcript level in cancer stage 1a (P=0.02) was observed. PELP1 protein content was higher in tumor tissues of patients with cancer stage 3a (P=0.04) and in T1a tumor size (P=0.03). Our studies demonstrate significantly higher amounts of PELP1 transcript and protein in tumor tissues in patients with NSCLC. Moreover, we also determined the association of PELP1 transcript and protein level with some clinicopathological features of NSCLC.