Herein, we reported that FBXW2 acted as a novel tumor suppressor in PCa by promoting the ubiquitylation and degradation of the oncogenic protein EGFR with following lines of supporting evidence: (1) FBXW2 is down-regulated in highly-metastasis PCa cells and tissues; (2) Enhanced FBXW2 significantly attenuates growth and metastasis of PCa models in vitro and in vivo; (3) EGFR is overexpressed in PCa cells, which has been demonstrated to contribute to growth and metastatic of PCa [27]. Here, FBXW2 is linked to neoplasm.