The discharge of azo-dye mols. in wastewater has raised significant environmental and health concerns. Therefore, the development of visible light-active photocatalysts to degrade the dye mols. in wastewater can be a promising solution In this study, CuxFeSx derivatives were synthesized by solvo-hydrothermal method with different solvents (deionized water (Wt), ethanol-Wt (Et-Wt) and Et) to investigate their photocatalytic activity towards Direct Red 80 (DR-80) and safety in human cell lines. The physicochem. properties of the synthesized products, including crystallinity, surface morphol. and chem. properties were characterized. The results showed that CuxFeSx-Wt and CuxFeSx-Et-Wt produced flower-like morphol. interconnected with nanosheets, while CuxFeSx-Et is produced a mixture of edged particles and nanosheets. Among them, CuxFeSx-Et exhibited the highest photocatalytic efficiency of DR-80 at 98.76% in 195 min, compared to CuxFeSx-Et-Wt (96.17% in 240 min) and CuxFeSx-Wt (93.32% in 285 min). CuxFeSx-Et also showed a high recyclability of 94.93%. The degradation of DR-80 dye followed the Langmuir adsorption model. Furthermore, the low cytotoxicity of CuxFeSx nanocomposites to human intestinal epithelial cell line (Caco-2) and human macrophage-like cell line (differentiated THP-1) suggests that these materials are benign. This study provides new insights into the benign-by-design of CuxFeSx as photocatalysts for the degradation of dye mols. in environmental remediation.