Recent evidence indicated ubiquitin like with PHD and ring finger domains 2 (UHRF2) was involved in various human diseases, especially in cancer, however, its roles in cancer are still in dispute. Here, we found UHRF2 expression was decreased in lung cancer tissues compared with adjacent normal tissues by referring to the Oncomine Database, which was further identified by immunoblotting and quantitative real-time polymerase chain reaction assays. Secondly, we found knockdown of UHRF2 in A549 and 95-D cell lines enhanced the capability of proliferation, invasion and migration, while forced UHRF2 expression inhibited NSCLC cells proliferation,invasion and migration. Mechanistically, dot-blot and western blot assays indicated that the level of UHRF2 was positively correlated with 5-hmC level by affecting ten-eleven translocation 2 (TET2) expression. Clinically, UHRF2 downregulation is significantly correlated with a malignant phenotype, including larger tumor size and poor differentiation. Moreover, UHRF2 downregulated correlates with shorter overall survival(OS). Conclusion: Our findings indicate that UHRF2 is a tumor suppressor in NSCLC by influence TET2 expression and serve as a potential therapeutic target in NSCLC.