Sex hormone-binding globulin (SHBG), a crucial modulator of sex steroids in human blood, regulates androgen bioavailability and homeostasis. When androgen or AR signaling is known to be involved in the hepatocellular carcinoma (HCC) and SHBG plays an integral role in regulating the levels of bioavailable androgens, the concern whether SHBG might influence HCC onset or progression by modulating androgen action remains open. Our study aims to investigate the role of SHBG in HCC progression in contexts of androgen regulation and steroid independence.