The purpose of the current research is to optimize the synthesis of sodium hyaluronatetitanium dioxide nanocomposite with the highest anticancer activity. To this end, the Taguchi method was followed to design nine experiments with different ratios of sodium hyaluronate biopolymer, titanium dioxide nanoparticles and stirring times. The results of scanning electron microscopy (SEM) confirmed the synthesis of the nanoparticle and nanocomposite. The comparison of anticancer activity level of synthesized nanocomposites using MTT assay showed that the nanocomposite synthesized in the conditions of experiment 9 (8 mg/ml of titanium dioxide nanoparticles, 2 mg/ml of sodium hyaluronate biopolymer and 60 min stirring time) had the maximum anticancer activity against Michigan Cancer Foundation-7 (MCF-7) cell line. According to the results, the Taguchi method can be employed as an effective and useful strategy to save time and cost in order to determine the optimal conditions for the synthesis of sodium hyaluronate-titanium dioxide nanocomposite with the most favorable anticancer activity.