In the present study, we detected the expression of Smurf2 in human HCC and adjacent non-tumor liver specimens, discussed the relationship between Smurf2 and clinicopathological features of HCC patients, and investigated the tumor-inhibiting effects of Smurf2 in vitro and in vivo, as well as its underlying mechanism involved with ubiquitination of Smad2. Here, SMURF2 is linked to hepatocellular carcinoma.