CSE1L is involved in the cancer progression of several types of cancer. Its expression status, potential oncogenic role and underlying mechanism in lung cancer, however, are unclear. Here, we investigated CSE1L expression in primary lung adenocarcinoma based on multiple datasets and then investigated its oncologic role in lung cancer. We also examined the potential molecular mechanisms of CSE1L in cancer progression. CSE1L levels were increased in cancer as compared to normal lung tissues. CSE1L expression was higher in poorly-differentiated late stage and lymph node positive metastatic tumors. Higher CSE1L level was correlated with worse patient outcome. Knockdown of CSE1L using siRNAs impaired cell proliferation, invasion, migration and induced cell apoptosis. Mechanistically, MET, STAT3 and PD-L1 proteins were decreased upon CSE1L silencing. These results suggest that CSE1L may affect tumor progression through MET/STAT3/PD-L1 signaling. CSE1L may have potential as a biomarker and therapeutic target for lung cancer.