A reduction-modified MoO3 catalyst is employed in the ethanolysis of Kraft lignin in supercritical ethanol. The reduction pretreatment under hydrogen atmosphere is carried out and shows a strong effect on the activity. A sample MoO3@623 K, that is, pretreated at 623 K, achieves the highest overall yield of small molecules, 1266 mg/g lignin. Compared with that using untreated MoO3 sample, the yield increases almost 15%, implying that the reduction pretreatment is effective for the enhancement of product yields and a promising strategy for industrial application. The XRD patterns and XPS spectra indicate that a transformation of bulk MoO3 to MoO2 happens at around 773 K, therefore, a MoO3@773 K catalyst gives a very low yield. The oxygen vacancies and Mo6+ together with Mo5+ formed during the partial reduction facilitate the formation of active species.