Metabolic dysfunction-associated steatohepatitis (MASH), for which there is almost no available medicine, could be a life-threatening disease. A lot of candidates have been tested in preclinical and clinical trials, such as Fc-FGF21 (Efruxifermin, Akero Therapeutics), which can reduce triglyceride significantly in MASH patients, but has little effect on low-density lipoprotein cholesterol (LDL-c) level. Several proprotein convertase subtilisin/kexin type 9 (PCSK9) antibodies which can reduce LDL-c have been approved for hypercholesterolemia, such as Alirocumab and Evolocumab. Protein engineering was used to construct a PCSK9 antibody and FGF21 conjugate. Physiochemical, in vitro and in vivo studies were finished to validate the roles of this candidate. We observed that PCSK9 antibody linked FGF21 had similar efficacy with positive control Fc-FGF21 in 3D NAC-Organ model and MASH mouse model. We also observed this conjugate had significant effect in humanized PCSK9 mouse, which had high level of LDL-c. This was the first report in which roles of PCSK9 antibody linked FGF21 were investigated together and candidate showed supposed dual functions in two different mouse models. Taken together, a candidate drug for MASH and hypercholesterolemia had been successfully developed. In future, animal study in monkey or human will be done to confirm its multifunctional efficacy and synergistic effect further.