OBJECTIVE: To investigate whether Lithospermum erythrorhizon polysaccharide inhibit the proliferation of H22 hepatoma solid tumor cells in mice through inducing autophagy. METHODS: 40 KM mice were randomly divided into model group, cyclophosphamide group (30 mg/kg, ip, once for every 4 d), L. erythrorhizon polysaccharide low-dose and high-dose groups (100, 300 mg/kg, ig, once a day), with 10 mice in each group. H22 hepatoma solid tumor model was induced of mice in each group by incubating H22 cell line. Treatment groups were given relevant medicine during modeling, and model group was given constant volume of normal saline intragastrically. After last medication, body weight, tumor weight coefficient, thymus and spleen index were recorded and determined. The mRNA expression of autophagy related genes, such as Atg5 and Beclin1, were measured by using Real-time PCR. The protein expression of autophagic microtubule-associated protein 3A/B (LC3A/B) was detected by Western blot assay. RESULTS: L. erythrorhizon polysaccharide could significantly reduce tumor weight coefficient of H22 solid tumor, with tumor inhibitory rate of 34.7%; it also significantly up-regulated the mRNA expression of autophagy related genes Atg5 and Beclin1 and the protein expression of LC3A/B, with statistical significance compared to model group (P<0.05 or P<0.01). CONCLUSIONS: L. erythrorhizon polysaccharide can inhibit the proliferation of H22 hepatoma solid tumor cells and slow down the growth of tumor through promoting hepatoma cell autophagy.