In this study, laccase produced by the white rot fungus strain Pycnoporus sp. Y1 was used for the leather dyeing wastewater decolorization. The mediators including veratryl alcohol (VA), 2,2’-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), hydroxybenzoic acid (HA), hydroxybenzotrizole (HOBT), and temperature, pH values, laccase concentration, and leather dyeing wastewater dilution ratio were all investigated in the experiments, and then four factors (mediators, temperatures, pH values, dilution ratios) were optimized by orthogonal experimental design. The optimal conditions for wastewater decolorization were obtained as follows: temperature of 50°C, pH 3.0, laccase concentration 4 U/mL, and the dilution ratio of 1-fold, the decolorization ratio could reach 58.42% in 10 min under the optimized conditions at last.