SENP1, a protein involved in de-SUMOylation, is a risk factor for tumor occurrence, recurrence and metastasis. It is associated with the occurrence, invasion, metastasis and drug resistance of a variety of tumors. Its expression in tumor tissues is of great significance. SENP1 contributes to the recurrence and metastasis of lung cancer by interacting with a variety of molecules and target proteins to regulate the cell cycle, promote the tumor angiogenesis, and participate in cellular iron death, etc. SENP1 is an affecting factor for the poor prognosis of lung cancer. In this paper, we reviewed the mechanism of SENP1 and its targeting proteins in tumor development, and their effects on drug resistance and prognosis of lung cancer.