OBJECTIVE To prepare quercetin-human serum albumin-nanoparticles （Que-HSA-NPs），and to evaluate the in vivo and in vitro inhibitory effects of Que-HSA-NPs on hepatic fibrosis of non-alcoholic steatohepatitis （NASH）. METHODS Que-HSA-NPs were prepared by desolvation-chemical cross-linking method ，their appearance characteristics were observed ，and their particle size ，polydispersity index （PDI），Zeta potential and drug loading were detected. Quercetin （Que）and Que-HSA-NPs were applied to murine HSC-T 6 cells. The effects of them on survival rate of HSC-T 6，mRNA expression of transforming growth factor β（TGF-β），Type Ⅰ collagen α1（COL1A1）and α-smooth muscle actin （α-SMA）were compared. Que and Que-HSA-NPs were applied to mice fed with low methionine and choline deficient high-fat diet. The serum levels of liver injury indexes ，liver pathological characteristics ，mRNA expressions of TGF-β，COL1A1 and α-SMA，protein expression of α-SMA in liver tissue were determined to evaluate the improvement effects of them on hepatic fibrosis of NASH in mice. RESULTS The prepared Que-HSA-NPs was spherical ，the particle size was （172.9±2.2）nm，the PDI was 0.233，the Zeta potential was －29.2 mV，and the drug loading was 2.99％. Que and Que-HSA-NPs were nontoxic to HSC-T 6 at concentrations of 0-250 μg/mL. Both of them could significantly decrease mRNA expressions of TGF-β，COL1A1 and α-SMA，especially Que-HSA-NPs （P＜0.05）. They also could significantly decrease the serum levels of liver inju ry index ，relieve liver injury and down-regulate mRNA expressions of TGF-β，COL1A1 and α-SMA and protein expression of α-SMA， especially Que-HSA-NPs （P＜0.05）. CONCLUSIONS Que- HSA-NPs is successfully prepared ，and confirm that its anti- NASH hepatic fibrosis effect is better than that of Que .