Solvent effects and catalyst stability were studied in the three-phase hydrogenolysis of the natural occurring lignan hydroxymatairesinol to matairesinol. To study the solvent effects, the reaction was carried out over a Pd/C catalyst in a variety of solvents, including ethanol, 2-propanol, tert-butanol, 2-pentanol, as well as in a mixture of 2-propanol and water (50:50, v/v). Over 70% of the hydroxymatairesinol was converted in 4 h when ethanol, 2-propanol, and 2-pentanol were used as solvents. The reaction was significantly retarded by mixing 2-propanol with water and the lowest activity was obtained in tert-butanol. Alcohols with shorter carbon chains were also interacting with the reactant resulting in lower selectivity; the byproducts 7-ethoxymatairesinol and 7-isopropoxymatairesinol were obtained in ethanol (the lowest selectivity) and in 2-propanol, respectively. Hydrogenolysis in 2-propanol over palladium impregnated activated carbon, and two Beta zeolites (H-Beta-300 and H-Beta-150, SiO2/Al2O3 molar ratio 300 and 150) was also investigated with respect to deactivation; consecutive experiments were performed with the catalysts being filtered, washed, dried, and re-reduced in between the runs. The catalysts were prone to deactivation caused by fouling; long chain alkanes and aromatic components were blocking the active sites. The decrease in activity was the largest for the Pd-H-Beta-300 catalyst.