Objective: To better understand the contribution of dysregulated DNA methyltransferase 1(DNMT1) expression to the progression and biology of clear cell renal cell carcinoma(ccRCC).Methods: We examined the differences in the expression of DNMT1 in 89 ccRCC and 22 normal tissue samples by immunohistochemistry. In addition, changes in cell viability, apoptosis, colony formation and invading ability of ccRCC cell lines(786-0 and Caki-1) were assessed after transfection with DNMT1 siRNA.Results: We found DNMT1 protein was significantly higher expressed in ccRCC than that of in no-tumor tissues(56.2% and 27.3%, respectively, P=0.018). The expression of DNMT1 was strongly associated with ccRCC tumor size, tumor pathology stage, histological grading, lymph node metastasis, vascular invasion, recurrence and prognosis. Moreover, knockdown of DNMT1 expression significantly inhibited ccRCC cell viability, induced apoptosis, decreased colony formation and invading ability.Conclusions: Expression of DNMT1 protein is increased in ccRCC tissues, and DNMT1 expression is associated with poor prognosis of patients. Experiments in vitro further showed DNMT1 played an essential role in proliferation and invasion of renal cancer cells. Moreover, targeting this enzyme could be a promising strategy for treating ccRCC, as evidenced by inhibited cell viability, increased apoptosis, decreased colony formation and invading ability. Objective: To better understand the contribution of dysregulated DNA methyltransferase 1 (DNMT1) expression to the progression and biology of clear cell renal cell carcinoma (ccRCC). Methods: We examined the differences in the expression of DNMT1 in 89 ccRCC and 22 normal tissue samples by immunohistochemistry. In addition, changes in cell viability, apoptosis, colony formation and invading ability of ccRCC cell lines (786-0 and Caki-1) were assessed after transfection with DNMT1 siRNA. Results: We found DNMT1 protein was significantly higher expressed in The expression of DNMT1 was strongly associated with ccRCC tumor size, tumor pathology stage, histological grading, lymph node metastasis, vascular invasion, recurrence and prognosis. Moreover, knockdown of DNMT1 expression significantly inhibited ccRCC cell viability, induced apoptosis, decreased colony formation and invading ability. Conclusions: Expression of Experiments in vitro further showed DNMT1 played an essential role in proliferation and invasion of renal cancer cells. Moreover, targeting this enzyme could be a promising prognosis of patients. ccRCC, as evidenced by inhibited cell viability, increased apoptosis, decreased colony formation and invading ability.