Abstract: DNA polymerase θ (Pol θ), the only eukaryotic DNA polymerase currently known to possess both helicase and polymerase activities, plays a crucial role in DNA double-strand break (DSB) repair pathway-microhomology-mediated end joining (MMEJ). The synthetic lethality of Pol θ in homologous recombination deficiency (HRD) tumors has garnered significant attention in recent years. And Pol θ has become one of the pivotal anticancer targets in the research and development of numerous domestic and foreign pharmaceutical companies. This paper systematically reviews the structure and function of Pol θ protein and the latest research progress of small-molecule inhibitors, which is beneficial for further development of more efficient and specific Pol θ-targeted inhibitors for precision treatment of HRD tumors.