We demonstrated catalytic removal of naphthenic acids in highly acidic crude oil over catalyst prepared by impregnating CoO-MoO3 on mesoporous γ-Al2O3, and its sulfidate-form treated via post-synthetic sulfidation treatment to increase activity at lower temperature. We used almost real highly acidic crude prepared mixing heavy Castilla crude oil and naphthenic acids; total-acid-number (TAN) of this feedstock was 2.192 mgKOH/g. Our target TAN of product was 0.5 mgKOH/g (requirement of conventional refinery industry). For optimizing reaction conditions, temperature, hydrogen-pressure, hydrogen-to-oil (H2/oil) ratio and liquid-hourly-space-velocity (LHSV) of feed were screened. The oxide-form catalyst reduced TAN to lower than 0.5 mgKOH/g for 82 h, under optimized condition (T = 350 °C, PH2 = 0.5 MPa, H2/oil = 25 Nm3/m3, and LHSVfeed = 10 h−1). After sulfidation, this catalyst achieved target TAN at lower temperature (250℃) for 72 h (PH2 = 4.0 MPa, H2/oil = 50 Nm3/m3, and LHSVfeed = 3 h−1). Mechanism study shows that the removal of naphthenic acids occurred mainly through decarboxylation, decarbonylation and hydrodeoxygenation.