The aim of this research was to clarify the relationship between Sp2 expression in HCC and clinicopathological features by detecting the expression of Sp2, TRIB3, and ERS marker protein GRP78 in HCC and adjacent non‐neoplastic tissues (ANT), further study the biological function of Sp2 in hepatoma cells by small interfering RNA (siRNA) transfection technology so as to clarify its influence on proliferation, apoptosis, and invasion of HCC cells, as well as explore its possible molecular mechanism. Here, TRIB3 is linked to hepatocellular carcinoma.