The present study revealed a mechanism of celastrol-alleviating HCC that celastrol could regulate the gut microbiota and liver bile acid metabolism, inhibit the interaction of FXR with RXRα in the liver, induce mTOR/S6K1-related cell cycle G0/G1 phase arrest, and eventually alleviate the proliferation of HCC (Figure 8). Here, NR1H4 is linked to hepatocellular carcinoma.