Catalytic hydrodenitrogenation (HDN) of isoquinoline (IQ) over Ni or Pd/C was studied at 200 °C and 300 °C under pressurized hydrogen. Two pathways of the HDN of IQ over Ni or Pd/C at 200 °C were found: one from saturated derivatives to ring-opened products (ROPs) and another from hydroaromatic derivatives to ROPs. Thirty five kinds of addition products (APs) were identified in the reaction mixtures and most of the APs seemed to be substituted on nitrogen atom. Compared to Ni, Pd/C-catalyzed reactions of IQ yielded more APs, especially at 300 °C.