Collectively, our findings revealed that IQGAP1 promoted HBV-mediated anoikis resistance and metastasis through Rac1-dependent ROS accumulation and activation of Src/FAK pathway, implicating IQGAP1 as both a potential therapeutic target and a predictor of survival in HBV-associated HCC patients. Here, RAC1 is linked to hepatocellular carcinoma.