Abstract: High expression of programmed death ligand-1 (PD-L1), which is a major co-inhibitory checkpoint-regulating protein, mediates immune evasion by multiple cancers. PD-L1 expression is intricately regulated at transcriptional, translational, and posttranslational levels. Posttranslational PD-L1 modification is emerging as an attractive field of cancer immunotherapy. The stability and biological functions of PD-L1 are tightly controlled by posttranslational modifications, including glycosylation, ubiquitination, phosphorylation, palmitoylation, and acetylation. In this review, we present an overview of recent progress in the study of PD-L1 posttranslational modifications and try to shed light on the field to improve PD-L1-dependent cancer immunotherapy strategies.