A significant decrease in the p‐Smad1/5/8 and Smad6 levels following the increase in the p‐Smad3 level was detected in the HUVECs pre‐incubated with HBV‐infected hepatoma cells compared with those pre‐incubated with HBV‐uninfected hepatoma cells. Here, SMAD1 is linked to hepatocellular carcinoma.