OBJECTIVE: To study the antitumor effect of phellinus linteus polysaccharide on sarcoma S180 cells in vivo and in vitro. METHODS: Sarcoma S180 cells in logarithmic growth period were selected, adding into 0 (blank control), 2, 4, 8 mg/mL phellinus linteus polysaccharide solution and respectively culturing for 12, 24, 36, 48 h. The in vitro proliferation inhibition rate of cells was determined by MTT method; its apoptotic morphology was observed by fluorescence staining and cell apoptosis rate was detected by flow cytometry. S180 tumor-bearing mice models were established and randomly divided into control group, phellinus linteus polysaccharide high-dose, medium-dose, low-dose groups (400, 200, 100 mg/kg), 10 in each group. Model mice were intragastrically administrated related medicined, once a day, for 12 d. Mice were executed after 24 h of last administration, tumor weight was determined, tumor inhibition rate was calculated. Immunohistochemistry was conducted to detect the tumor suppressor gene PTEN and oncogene C-myc protein expressions in tumor tissue. RESULTS: Compared with blank control group, phellinus linteus polysaccharide can increase the proliferation inhibition rate of S180 cells and induce the increase of apoptosis rate (P<0.05 or P<0.01), showing a concentration-time manner. Compared with control group, the tumor inhibition rates in phellinus linteus polysaccharide groups were obviously increased (P<0.01), PTEN protein expressions were strengthened (P<0.05 or P<0.01) and C-myc protein expressions were weakened (P<0.05). CONCLUSIONS: Phellinus linteus polysaccharide shows antitumor effect in vivo and in vitro, which can up-regulate the PTEN, down-regulate C-myc protein expressions.