OBJECTIVE Polo-like kinase 4 (PLK4) is a serine/threonine protein kinase that regulates centriole duplication. PLK4 deregulation causes centrosome number abnormalities, mitotic defects, chromosomal instability and, consequently, tumorigenesis. Therefore, PLK4 has emerged as a therapeutic target for the treatment of multiple cancers. In this review, we summarize the critical role of centrosome amplification and PLK4 in cancer. We also highlight recent advances in the development of PLK4 inhibitors and discuss potential combination therapies for cancer. METHODS The relevant literature from PubMed is reviewed in this article. The ClinicalTrials.gov database was searched for clinical trials related to the specific topic. RESULTS PLK4 is aberrantly expressed in multiple cancers and has prognostic value. Targeting PLK4 with inhibitors suppresses tumor growth in vitro and in vivo. CONCLUSIONS PLK4 plays an important role in centrosome amplification and tumor progression. PLK4 inhibitors used alone or in combination with other drugs have shown significant anticancer efficacy, suggesting a potential therapeutic strategy for cancer. The results of relevant clinical trials await evaluation.