Control of cell cycle progression plays a significant role in tumor development. The cyclin-dependent kinase (CDK) family governs cell cycle progression, and the activations of CDK4 and CDK6 allow cells to transit from G1 phase to S phase to start mitosis. Overactivation of CDK4/6 is closely related to tumor progression, thus CDK4/6 can be used as a potential target of oncotherapy. CDK4/6 inhibitors can not only arrest the tumor cells at G1 phase to prevent tumor overgrowth, but also affect the tumor microenvironment and enhance immune activity. Trilaciclib is a small-molecule CDK4/6 inhibitor, which is highly efficient, selective and reversible. Trilaciclib administrated before chemotherapy can temporarily block the hematopoietic stem cells and progenitor cells in bone marrow at G1 phase to reduce the cytotoxic damage caused by chemotherapy, thus protecting bone marrow and the immune system. Trilaciclib was first approved by FDA in the United States in February 2021 for extensive stage small cell lung cancer (ES-SCLC) before platinum/etoposide or topotecan chemotherapy to reduce the incidences of myelosuppression in adult patients. In July 2022, National Medical Products Administration (NMPA) also approved the administration of trilaciclib in patients with ES-SCLC who had not previously received systemic chemotherapy. In addition, the positive effects of trilaciclib on overall survival (OS) were observed in patients with triple-negative breast cancer (TNBC) treated with chemotherapy. Other clinical studies related to trilaciclib were still ongoing. This review summarizes the anti-tumor mechanisms of trilaciclib and the relative preclinical and clinical studies, aiming to provide further reference for clinical application and future research.