In order to explore the changes of main active substances in Lactobacillus rhamnosus fermentation of Ganoderma lucidum fruitum powder and its inhibitory effect on hepatoma cell HepG2， a solid fermentation method was used to prepare the fermented Ganoderma lucidum fruitum powder with Lactobacillus rhamnosus as fermentation strain and Ganoderma lucidum fruitum powder as fermentation substrate， and its main active ingredients and antioxidant capacity were studied. Plant metabolomics of Ganoderma lucidum fruitum powder was determined and its surface structure was observed by scanning electron microscopy. The inhibitory effect of Ganoderma lucidum alcohol extract on hepatocellular carcinoma cells was detected by CCK-8 method. The effect of Ganoderma lucidum alcohol extract on hepatocellular carcinoma cell migration was detected by cell scratch method. Hoechst 33258 detected the effect of Ganoderma lucidum alcohol extract on cell nucleus and verified the apoptosis effect. The expression of apoptosis-related genes in HepG2 cells was analyzed by PCR. The results showed that the contents of triterpenoids and polysaccharides were 4.075 mg/g， 2.347 g/100g and 4.604 mg/g respectively compared with those before fermentation. The antioxidant capacity of Lactobacillus rhamnosus fermented Ganoderma lucidum powder was significantly improved compared with the original Ganoderma lucidum powder and fermented control Ganoderma lucidum powder. The results of plant metabolomics showed that the material composition and peak area of the three samples were significantly different. Cell test results showed that the ability of fermented Ganoderma lucidum alcohol extract to inhibit HepG2 cell growth and block cell migration was significantly increased， and the apoptosis was more significant in Hoechst 33258 results. PCR test confirmed that the intervention of fermented Ganoderma lucidum alcohol extract significantly up-regulated the apoptosis-related genes Bax， Cyclin-A， CDK-2， P21 and P53， and significantly down-regulated the apoptosis-related genes Bcl-2. Conclusions: Lactobacillus rhamnosus fermentation of Ganoderma lucidum can increase the contents of main active substances， such as triterpenoids， polysaccharides and flavonoids of Ganoderma lucidum， and the ethanol extract of Ganoderma lucidum fermentation has stronger inhibitory effect on HepG2 cells.