Autophagy plays an important role in liver triglyceride (TG) metabolism. Inhibition of autophagy could reduce the clearance of TG in the liver. Hydrogen sulfide (H₂S) is a potent stimulator of autophagic flux. Recent studies showed H₂S is protective against Hypertriglyceridemia (HTG) and noalcoholic fat liver disease (NAFLD), while the mechanism remains to be explored. Here we test the hypothesis that H₂S reduces serum TG level and ameliorates NAFLD through stimulating liver autophagic flux by AMPK-mTOR pathway. The level of serum H₂S in patients with HTG was lower than that of control subjects. Sodium hydrosulfide (NaHS, H₂S donor) markedly reduced serum TG levels of male C57BL/6 mice fed with high-fat diet (HFD), which was abolished by co-administration of chloroquine (CQ), an inhibitor of autophagic flux. In HFD mice, administration of NaSH increased LC3BII to LC3BI ratio, decreased p62 protein level. Meanwhile, NaSH increased the phosphorylation of AMPK, and thus reduced the phosphorylation of mTOR by western blot study. In cultured LO2 cells, high fat treatment reduced the ratio of LC3BII to LC3BI and the phosphorylation of AMPK, which were reversed by the co-administration of NaSH. Knockdown of AMPK by siRNA in LO2 cells blocked the autophagic enhancing effects of NaSH. The same qualitative effect was observed in AMPKα2^-/-mice. These results for the first time demonstrated that H₂S could reduce serum TG level and ameliorate NAFLD by activating liver autophagy via AMPK- mTOR pathway.