The heterogeneous Fenton-type process was investigated in a continuous upflow fixed-bed reactor (UFBR) of a nano Prussian Blue catalyst supported on γ-alumina beads. Temperature and oxidant concentration strongly increased dye discoloration and total organic carbon (TOC) conversion. The long-term stability of the catalyst was confirmed. The best performance was found with a residence time of 2 min at 353 K and an inlet hydrogen peroxide concentration twice the stoichiometric one required for mineralization, attaining complete discoloration and 45% TOC conversion. The formed reactive species continued the reaction after leaving the UFBR. Hydrodynamic cavitation (HC) of the collected outlet stream led immediately to complete discoloration and doubled the TOC conversion in 40 min. Short-chain carboxylic acids accounted for about 70% of the remaining TOC. The UFBR in-series with the HC reactor led to complete discoloration and intensified the TOC conversion. The subsequent HC step thoroughly consumed the remnant oxidant, increasing its efficiency.