In this research, the non-formaldehyde wrinkle-resistant treatment of cotton fabrics has been investigated using the citric acid (CA) as a cross-linking agent and sodium hypophosphite (SHP) as a catalyst together with nano-titanium dioxide (nano-TiO₂) as a co-catalyst compound. The effect of the changes in the concentrations of CA, SHP, and nano-TiO₂ on the wrinkle recovery angle (WRA), tensile strength, tearing strength, whiteness index, and flexural rigidity of cotton fabrics was studied using Box–Behnken design. It was found that the addition of nano-TiO₂ could enhance the wrinkle resistance and decrease the flexural rigidity of the cotton fabric with little effect on the whiteness index, and tearing and tensile strengths of the treated fabric. The developed empirical models are found to be in good correlation with the selected variables (r²≥ 0.8). From this study, it was concluded that 10% CA, 10% sodium dihydrogen phosphate, and 0.1% nano-TiO₂ were the optimum concentrations required to enhance the WRA without adversely affecting the other physical properties of the treated cotton fabrics.