Background: Azo dyes are widely used recalcitrant chemicals and may promote environmental hazard. Amongst the known azo dyes is CI Direct Red 28 (C32H22N6Na2O6S2) aka Congo Red (CR), which is a known mutagen and carcinogen. In this sense, this work aimed the biodegradation of a CR-containing synthetic effluent, and the evaluation of the ecotoxicity of post-treatment residues. Methods: Lentinus crinitus Laccase (Lac)-mediated bioremediation of CR was optimized upon added concentrations of sucrose and CuSO4, moreover a standard ecotoxicity assay was performed. Results: Results showcased that the addition of 5% sucrose and 2 mM CuSO4 increase CR degradation, being Lac activity at 48 h of 30.2 U mL-1, and at 72 h of 31.9 U mL-1. Moreover, the ecotoxicity assay showcased that CR degradation by L. crinitus Lac seemingly generated low ecotoxic byproducts. Conclusion: Given that CR bioremediation byproducts were known to exhibit high toxicity, our results shed light on the use of L. crinitus catalytic arsenal to promote proper remediation of azo dye-polluted effluents.