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Modification of silk fabric via grafting with β-cyclodextrin (β-CD) using citric acid (CA) as a cross-linking agent was studied and optimized. A four-factor central composite design combined with response surface methodology (RSM) was employed to optimize the reaction conditions (CA and β-CD concentration, curing temperature, and time) for preparation of β-CD modified silk fabric with a maximum degree of grafting yield and minimum strength loss and minimum yellowness Index. Analysis of variance (ANOVA) proposed a significant quadratic model for optimizing of grafting factors. From the obtained results, it is concluded that CA concentration and curing temperature had a greater influence on grafting yield than curing time and CD concentration. The optimum grafting condition was obtained at β-CD concentration: (57 g/L), CA concentration: (57 g/L), curing temperature: (167°C), and curing time (4 min) which results grafting of CD equal to 10%.