Renal clear cell carcinoma (ccRCC), is an inflammation-related malignancy with poor therapeutic outcome. Interferon-induced transmembrane protein 2 (IFITM2), an inflammation related gene, is reported to promote tumor progression via inducing cytokine release and lymphatic metastasis. However, IFITM2's role in ccRCC remains unclear. In this study, we aimed to explore the role of IFITM2 in ccRCC. In vitro studies displayed overexpressed IFITM2 level in tumor tissues, while analysis of 538 cases from TCGA unveiled the correlation of upregulated-IFITM2 with shorter survival. Migration and invasion of ccRCC were inhibited following the downregulation of IFITM2. Cocultured with IFITM2-silenced ccRCC cells, human lymphatic endothelial cells were inhibited in proliferation, migration and tube formation, indicating that lymphangiognesis was contributed by IFITM2 expression. Taken together, IFITM2 promotes ccRCC progression by inducing malignant characteristics and lymphatic metastasis. Therefore, IFITM2 represents a promising novel target for therapy and effective prediction of malignancy of ccRCC. (C) 2020 The Authors. Published by Elsevier Inc.