Lignocellulosic biomass is a promising alternative to petroleum oil for producing energy and chemicals, owing to its abundance and sustainability. In the past decades, extensive research has applied a wide range of thermo-chemical technologies for converting biomass into value-added products. Among them, hydrothermal liquefaction (HTL) is regarded to be one of the most effective techniques to produce bio-fuels and bio-based chemicals. However, there are still several technical barriers that must be addressed before the industrialization of HTL technology. Although many previous reviews have summarized the reaction mechanism, properties of liquefaction products, and various operating parameters, few articles have discussed the potential applications of HTL products and the techno-economic problems facing by the industrialization of HTL. Therefore, in this review, the possible applications of HTL products (bio-crude, aqueous phase, solid residue, and gas) were thoroughly discussed. In addition, the current challenges of HTL treatment, especially for the continuous operation, to produce bio-based fuel and chemicals is reviewed. Finally, the possible future directions and the main conclusions are covered. •The benefits and weaknesses of using water as the reaction medium are presented.•The characteristics and potential applications of HTL products are discussed.•Beside bio-crude, by-products from HTL could bring value to HTL.•Critical challenges to the continuous operation of HTL are identified and discussed.