With the depletion and increasing exploitation of fossil energy, it is necessary to develop renewable and alternative fuels. As the most abundant component of lignocellulosic biomass, cellulose can be converted into monosaccharides or other chemical platform molecules, which brings the potential for the sustainable production of chemicals and fuels. In the process of cellulose conversion, acid catalysts can promote hydrolytic degradation of cellulose into valuable platform compounds, which is of great significance in the development of chemicals and biofuels. Among the acid catalysts, heteropolyacid (HPA) as a green catalyst has extraordinary acidity, which is more conducive to the degradation of cellulose biomass. More importantly, HPAs can be designed in the heterogeneous systems that impel them to be easily separated from the products by some simple extraction processes. Compared with homogeneous catalysts, heterogeneous catalysts have some obvious advantages, such as easy separation and wide application. According to the unique properties of HPAs (e.g., strong acidity, high thermal stability, and good solubility), it has become one of the most significant processes of sustainable development in chemistry to use heteropolyacid-based catalysts to depolymerize cellulose and further convert it into high value-added chemicals and biofuels. In this chapter, the advantages, characteristics, and applications of HPAs in different categories for cellulose degradation, especially hydrolysis degradation, are summarized. Moreover, the mechanisms of heterogeneous HPA catalysts in the effective degradation of cellulosic biomass are discussed. This chapter provides more ways to develop new and high-performance heterogeneous HPA catalysts for cellulose degradation in the future. © 2022 Elsevier Inc. All rights reserved.