The influence of co-solvents on hydrothermal liquefaction (HTL) of Fallopia Japonica was studied as a function of temperature. Combination of low and high-resolution mass spectrometry with multi-layered data mining strategy resulted in a comprehensive characterization of the reaction products, mostly water-soluble organics (WSO) with a broad spectrum of chemical functionalities. The non-targeted analysis revealed the presence of a core composition in the samples independent of the process conditions and consisting of hydroxycarboxylic acids, imids, lactones, lactams, phenolics, various short-chain oxygenated aliphatics, and cyclohexane derivatives. Changes in process conditions did not affect those species showing that a part of the HTL product is not susceptible to process tailoring by addition of co-solvents. The findings indicated that the effect of tetralin is a combination of solubilization and scavenging resulting in an increased abundance of monomeric aromatics. For acetone, the results pointed to the promotion of retro-aldol splitting yielding low molecular weight oxygenates.