Anaerobic digestion is a possibility for post-hydrothermal liquefaction wastewater (PHWW) treatment because this wastewater is rich in nutrients and organic compounds. However, the PHWW presents many toxic compounds. A strategy for the anaerobic treatment of toxic compounds is using biomass adhered to inert supports forming biofilms, which can offer more resistance to the microorganism and protection from such compounds. The continuous treatment of PHWW is the essential key to obtaining a sustainable hydrothermal liquefaction process. In this work, the use of immobilized biomass was evaluated for the anaerobic degradation of PHWW from Spirulina in batch assays and continuous treatment. Higher methane production potential and volatile fatty acid mass balance showed the advantages of using biomass immobilized in polyurethane foam. Continuous treatment in a horizontal-flow anaerobic immobilized biomass (HAIB) reactor reached chemical organic demand (COD) removal efficiencies of 67% and 58% for volumetric organic load rates of 0.8 and 1.6 g COD.L−1.d−1, respectively. After 200 days of continuous treatment, Anaerobaculum and Coprothermobacter, fermentative proteolytic genera of bacteria with potential for hydrogen production, were favored.