OBJECTIVE: To analyze the expression levels of EGFR, ERCC1, TUBB3, TYMS, and RRM1 of patients with adenocarcinoma non-small cell lung cancer (NSCLC) and the molecular biological significance, so as to provide a reference for combined chemotherapy of advanced lung cancer. STUDY DESIGN: A total of 123 adenocarcinoma NSCLC patients with malignant pleural effusions were selected to detect the expression levels of EGFR, ERCC1, TUBB3, TYMS, and RRM1 using immunocytochemistry and real-time quantitative PCR. RESULTS: There was no statistically significant difference in the mRNA expression levels of genes among other patients with different characteristics except for smokers and nonsmokers (p > 0.05). The negative expression rate of EGFR in malignant pleural effusion was 0.3%, the weak positive expression rate was 17.1%, the positive rate was 40.7%, and the strong positive expression rate was 34.8%. The positive expression rates of ERCC1, TYMS, TUBB3, and RRM1 were 41.5%, 42.3%, 67.5%, and 74.0%, respectively. With different intensities of EGFR expression, ERCC1, TYMS, and TUBB3 had significantly different protein expression rates. CONCLUSION: Chemotherapy regimens can be selectively developed according to different expression levels of EGFR, ERCC1, TUBB3, TYMS, and RRM1 in clinical practice, aiming to provide effective treatment for patients with adenocarcinoma NSCLC. © Science Printers and Publishers, Inc.