Herein, a novel nanohybrid composite of magnetic chitosan-salicylaldehyde/nanoclay (MCH-SAL/NCLA) was hydrothermally synthesized for removal of azo dye (acid red 88, AR88) from simulated wastewater. Response surface methodology combined with the Box-Behnken design (RSM-BBD) was applied with 29 experiments to assess the impact of adsorption variables, that include A: % NCLA loading (0–50), B: MCH-SAL/NCLA dose (0.02–0.1 g/100 mL), C: pH (4–10), and time D: (10–90 min) on AR88 dye adsorption. The highest AR88 removal (75.16 %) as per desirability function was attained at the optimum conditions (NCLA loading = 41.8 %, dosage = 0.06 g/100 mL, solution pH = 4, and time = 86. 17 min). The kinetic and equilibrium adsorption results of AR88 by MCH-SAL/NCLA reveal that the process follows the pseudo-first-order and Temkin models. The MCH-SAL/NCLA composite has a maximum adsorption capacity (173.5 mg/g) with the AR88 dye. The adsorption of AR88 onto the MCH-SAL/NCLA surface is determined by a variety of processes, including electrostatic, hydrogen bonding, n-π, and n-π interactions. This research revealed that MCH-SAL/NCLA can be used as a versatile and efficient bio-adsorbent for azo dye removal from contaminated wastewater.