Abstract: Cell cycle turnover depends on cyclin-dependent kinase (CDKs). CDK is the protein kinase family that plays the key role in regulating cell cycle and gene transcription. CDK12 and CDK13 perform the essential work in DNA damage response, RNA splicing regulation, transcription, and cell cycle regulation. In recent years, CDK12 and CDK13 are expressed abnormally or mutated in a variety of cancers; thus, they are necessary in cancer development and have become popular topics of research. Based on literature from Google Scholar, PubMed, and WanFang database, aspects of CDK12 and CDK13 such as basic structure, biological function, correlation with malignant tumors, and research progress of targeted inhibitors are summarized to provide the direction for the subsequent research of the new targets and mechanisms for targeting therapy while offering a novel approach for the prevention, diagnosis, and treatment of malignant tumors in the future.