The changes in cell homeostasis in the tumor microenvironment may affect the development of colorectal cancer (CRC). Genomic instability is an important factor. Persistent genomic instability leads to epigenetic changes, and mutations are a major factor in the progression of CRC. Based on these mechanisms, it is reasonable to link poly (ADP-ribose) polymerase (PARP) with the treatment of colorectal cancer. PARP is mainly involved in DNA repair, which has an essential role in the DNA damage response and prevention of DNA damage, and maintains oxidation and superoxide redox homeostasis in the intracellular environment of the tumor. This article reviews the latest research progress on PARP and PARP inhibitors (PARPi) in CRC. It mainly includes molecular mechanisms, immunity, clinical trials, and combination strategies of CRC. The research of PARPi in CRC has broad prospects, and the combinations with other drugs are the main research direction in the future.