The purpose of the study covered in this paper was to probe into the inhibitory effect of tetrandrine on HepG-2 hepatocellular carcinoma cells by destroying tumor cell membrane function. The CCK-8 results indicated that tetrandrine caused significant reduction on the proliferation of HepG-2 cells. While observed with fluorescent microscopy and inverted microscopy, morphological alterations caused by apoptosis were identified subsequent to tetrandrine administration. Compared with control group, the tetrandrine treatment group had significantly elevated apoptosis rate, according to flow cytometry. In addition, changes of membrane functional components (protein, cholesterol, and sialic acid) were detected. Cell membrane fluidity was measured by fluorescence polarization. Blocking degree of HepG-2 cells membrane was measured by chromameter. Results showed that tetrandrine could reduce the functional components of tumor cell membranes and decrease the fluidity and blocking degree of HepG-2 cell membrane. Meanwhile, tetrandrine could decrease the activities of Na+/K+-ATPase and Ca2+/Mg2+-ATPase was also observed by ATPase activity assay. Tetrandrine significantly down-regulated GLUT-1 and LAT-1 levels and compared with control group, according to western blot assay findings. In conclusion, tetrandrine can reduce the fluidity and blocking degree of cell membrane by reducing the content of total protein, cholesterol and sialic acid content of HepG-2 cells. Moreover, it can destroy the homeostasis of tumor cell internal environment, reduce the supply of cell nutrients by reducing the activity of ion transporters, down-regulating the expression of glucose and amino acid transporter, and ultimately all the above facilitate the trigger of apoptosis of malignant HepG-2 cells.