Nintedanib (ND) was known as a triple tyrosine kinase inhibitors, inhibiting angiogenesis and tissue fibrosis. Biguanide group has attracted much attention for its great penetrating ability to the lipid bilayer of cytomembrane and potential anti-cancer efficacy. In this study, a biguanide group (p-biguanidinobenzoic acid, CBH) decorated bovine serum albumin (CBH-AB) was synthesized as a novel functional biomaterial to prepare the ND loaded CBH-AB nanoparticles (ND-CBH-AB NPs). The results of physical and chemical properties showed that ND-CBH-AB NPs possessed high encapsulation efficiency and drug loading efficiency. In vitro cell study indicated that CBH modification on ND-CBH-AB NPs enhanced the cyctotoxicities to HepG2 cells. Furthermore, pharmacokinetic study showed that ND-CBH-AB NPs had good stability in circulation. Finally, pharmacodynamic studies were conducted, the results indicated that ND-CBH-AB NPs exhibited excellent anti-tumor effect and tumor microenvironment regulation effect. Thereby, this work provides a potential function albumin delivery system for hepatocellular carcinoma therapy.