Aim. In recent decades, immunotherapy has become important for treating the non-small cell lung cancer (NSCLC) patients. However, specific genetic alterations limit the response to immune checkpoint inhibitors even in the presence of PD-L1 expression. The study aimed to evaluate the relationship between genetic disorders in the EGFR and ALK genes and PD-L1 expression in NSCLC patients. Conclusions. Mutations in the EGFR gene and ALK rearrangement are associated with the activation of PD-L1 expression. Therefore, mandatory molecular testing to personalize the treatment of NSCLC patients is needed.