The morbidity and mortality of lung cancer in Xuanwei, China, are the highest in the world. This study attempts to identify differentially expressed genes (DEGs) related to lung adenocarcinoma in Xuanwei. The expression profiles of eight paired lung adenocarcinoma tissues and corresponding nontumor tissues were acquired by microarrays. Functional annotations of DEGs were carried out by bioinformatics analysis. The results of the microarrays were further verified by real-time quantitative PCR (RTq-PCR). A total of 5290 genes were classified as DEGs in lung adenocarcinoma in Xuanwei; 3325 genes were upregulated and 1965 genes were downregulated, whereas the expression of the other 11970 genes did not change. These DEGs are involved in a wide range of cancer-related processes, which include cell division, cell adhesion, cell proliferation, and DNA replication, and in many pathways such as the p53 signaling pathway, the MAPK pathway, the Jak-STAT signaling pathway, the hedgehog signaling pathway, and the non-small-cell lung cancer pathway. The tendency of changes in the expression of 12 selected DEGs (five downregulated genes, PIK3R1, RARB, HGF, MAPK11, and SESN1, and seven upregulated genes, PAK1, E2F1, CCNE1, EGF, CDC25A, PTTG1, and UHRF1) in RTq-PCR was consistent with the expression profiling data. Expression of PAK1 was significantly increased in the low differentiation group (P=0.031), whereas expression of HGF was significantly decreased in the low differentiation group (P=0.045). RARB and MAPK11 were significantly increased in the nonsmoker group (P=0.033 and 0.040, respectively). A large number of DEGs in lung adenocarcinoma in Xuanwei have been detected, which may enable us to understand the pathogenesis and lay an important foundation for the prevention and treatment of lung adenocarcinoma in Xuanwei.