The present study reports about the development of heterogeneous Fenton process by means of nano zero-valent iron particles (nZVI) as heterogeneous catalyst for the treatment of a synthetic tannery wastewater (STW). The experimental tests were conducted using a pilot Fenton plant for the investigation of the scale-up possibility of the treatment process, studying the influence of initial pH (varied in the range 3-7) and catalyst/oxidant ratio (Cat/Ox wt%) on the overall efficiency of the process. The target wastewater prepared in laboratory, was characterized by a high initial COD0=1200 mg/L and the monitored parameters during the process were COD and hexavalent chromium (Cr(VI)) concentrations. Two different Cat/Ox ratios were tested (20 and 35%) whereas the H2O2 amount was fixed equal to 0.75*COD0. The treatment process was performed for the first 2 h in batch, whereas the remaining 8 h were conducted in continuous. The optimal operating parameters (Cat/OX=35%, pH=3) allowed to reach a COD removal efficiency of 70% and a total Cr(VI) removal.