Exposure to ultraviolet light has a negative impact, including skin disorders to skin cancer. One way to overcome the negative effects of ultraviolet light is sunscreen protection. Active sunscreen ingredients used are 2-hydroxy-4- (octyloxy)benzophenone (HOB) as chemical UV filters and titanium dioxide (TiO2) as physical UV filters. The combination of chemical UV filter with physical UV filter can increase the SPF value so that it can protect skin health from maximum exposure to ultraviolet light. Sunscreen is made in the form of cream. One way to determine the combination of HOB with TiO2 needs to be done formula optimization. This study aims to determine the effect of a combination of cream preparations on the SPF value, determine the physical properties of cream preparations, and determine the optimum concentration of cream preparations. The test results of the physical properties of cream preparations showed organoleptic observations, pH measurements, homogeneity tests, and viscosity tests fulfilling the requirements. Adhesion test and dispersion test do not meet the requirements. Stability test both room temperature storage and cycling test cream preparations are less stable. Formula optimization is done by using the D-optimal Mixture Design with 2 independent variables namely HOB and TiO2 with a concentration limit of each variable 5-10%. The response used is viscosity and SPF value. The response results obtained from 7 runs produce viscosity with a range of 7853,339756.66 cps and SPF values with a range of 4,1406,389. ANOVA analysis results show significant results on both responses. The optimum formula results from the predicted D-optimal Mixture Design obtained a 10% HOB concentration and 5% TiO2. One-Sample T Test analysis results show the results of the optimum formula with the predicted D-optimal Mixture Design results are valid because they do not experience significant differences.