Objective: To study effects of Hippophae rhamnoides polysaccharides(SBP-3) on proliferation， apoptosis， invasion of Hep-G2 cells through p38 pathway. Methods: The proliferation of Hep-G2 cells was detected by CCK-8 method. The apoptosis of Hep-G2 cells was detected by flow cytometry. The migration and invasion of Hep-G2 cells were detected by scratch test and Transwell method. The effect of seabuckthorn polysaccharide on Hep-G2 cells was investigated by Western blot. Results: After 48 hours of SBP-3 treatment， the inhibition rate of each group(125， 250， 500， 1 000 μg/mL)was significantly increased (P<0.05)， and the highest inhibition rate was 60.43% at the concentration of 1 000 μg/mL. Apoptosis of Hep-G2 cells could be induced in each dose group(125， 250， 500 μg/mL) (P<0.01)， and the apoptosis rate gradually increased with the increase of SBP-3 concentration. At the same time， SBP-3 can weeken the invasion and migration ability of cells(P<0.01)， inhibit MMP-2 and MMP-9 protein expression (P<0.01)in p38 signaling pathway. Conclusion: SBP-3 can inhibit the proliferation， apoptosis， migration and invasion of Hep-G2 cells. It is speculated that SBP-3 can further inhibit the expression of MMP-2 and MMP-9 by down regulating the activity of p38MAPK signaling pathway.