Background: The expression of PD-L1 is closely related to the curative effect. Here, we want to study the details of gene mutation in expression and dig out some relevant information from Chinese LC patients. Methods: LC patients with both genomic information and PD-L1 expression status were screened from HapLab database. PD-L1 expression was detected by immunochemistry. R packages ClusterProfiler was used for gene enrichment analysis. Results: LC Patients were divided into two groups by tumor proportion score (TPS):1039 PD-L1 negative patients (TPS < 1%) and 1669 PD-L1 positive patients (TPS > = 1%). The overall mutation frequency of 51 genes were significantly different between PD-L1 negative patients and PD-L1 positive patients (Chi-Squared test, Pvalue < 0.05). 6 genes were mutated at high frequencies in patients with high TPS, and 45 genes were mutated at high frequencies in patients with low TPS. Among these genes, FGFR3, MDM2 and SKT11 have been reported to be associated with HPD, showing significantly higher mutation frequencies in PD-L1 negative patients (Pvalue < = 0.001). Two sets of genes were enriched respectively, both of which were enriched in MAPK and PI3K-Akt related pathways, while the enrichment results of EGFR tyrosine kinase inhibitor resistance only existed in PD-L1 negative. Conclusions: Our study investigated the genomic alterations associated with PD-L1 expression status in Chinese LC patients. From the data of Chinese lung cancer patients, we found 55 genes related to PD-1/PD-L1 treatment. These genes contain HPD related genes. Perhaps PD-L1 expression is associated with HPD.