Abstract: G protein-coupled receptor kinases (GRKs) are involved in a wide range of cellular physiology and pathological activities by specifically phosphorylating activated G-protein coupled receptors (GPCRs) to terminate GPCR signaling and phosphorylating non-GPCR substrates. Although significant progress has been made in the study of the relationship between GRKs and tumor pathogenesis in recent years, the detailed molecular mechanism needs to be further elucidated. This article discusses the diverse role of non-rhodopsin GRKs in the regulation of a variety of tumor cells, with the goal to provide new ideas for further research in this field.