Lignocellulosic residues are an interesting alternative to produce furans as 5-hydroxymethylfurfural (HMF), which can be oxidized to produce 2,5-furandicarboxylic acid (FDCA). According to the latter, this research aims to optimize the oxidation yield of HMF to FDCA catalyzed by a Trametes versicolor laccase using TEMPO as a mediator. For yield optimization, a Box–Behnken experimental design was developed with three factors and three levels. The model achieved 90 % fit (R2) with a maximum yield of 100 % FDCA, using 30 mM HMF, 55 mM 2,2,6,6-Tetramethylpiperidine 1-oxyl (TEMPO), and 6 mg laccase. The oxidation kinetics (at 30 and 100 mM HMF) evidenced the presence of the intermediate compound 5-formyl-2-furancarboxylic acid (FFCA), being higher when working at a higher concentration of substrate (100 mM HMF). Optimizing the operational conditions resulted in a notable improvement, boosting the yield of FDCA by approximately 10 % compared to the initial experimentation. Finally, the values of the variables predicted by the program were validated experimentally, reaching 100 % performance.