The removal of Direct Blue 71 (DB71), by laccase (EC 1.10.3.2, p-bezenediol:dioxygen oxidoreductases) enzyme in presence of 2,2′-Azinobis-(3-ethylbenzothiazoline-6-sulfonate) (ABTS), in aqueous solution was investigated. Data on this article focused on the optimizing and modeling of DB71 removal by Response surface method (RSM) based on Box–Behnken design (BBD), through studying the effective variables as follows: ABTS dose (0.05–0.2 mM), Laccase dose (0.05–0.2 U mL−1), and pH (3–7). The results of experimental showed that laccase was able to removal DB71 with removal percentage of 83% at concentration of 50 mg L−1 after 30 min incubation in presence of ABTS 0.2 mM, at temperature 40 °C and pH 5. The Analysis of Variance (ANOVA) for the predicted quadratic model was done and quadratic equation showed significant R-Squared (0.9969), Adjusted R-Squared (0.9914) and Adequate Precision (49.7). The lack of fit is not significant due to p-value prob > F more than 0.05.