Orange Fleshed Sweet Potato (OFSP) tuber is a rich source of β-carotene with potential antioxidants and phenolic compounds, nevertheless it is highly perishable root crop. Hence, we considered the optimization of parameters for the preparation of OFSP powder in spray drying technique. This study was designed by the Response Surface Methodology (RSM) with three factors in three levels considered in Central Composite Design (CCD). In case of spray drying process specification, inlet air temperature (IAT) (150 °C-190 °C), flow rate (FR) (10-20 ml/min), and carrier (Maltodextrin) concentration (MDC) (5-15%) were considered and optimized for better quality OFSP powder. As concentration of maltodextrin increased the powder yield, solubility, β-carotene content of OFSP powder increased, while hygroscopicity is decreased. The optimized conditions comprised of an inlet temperature of 172.71 °C, feed flow rate of 20 ml/min, and maltodextrin of 1% concentration. Under this optimized conditions, OFSP powder yield of 48.460%, with the solubility of 26.839%, β-carotene of 25.823 mg/100 g and minimum hygroscopicity of 13.862% was attained. The SEM images of spray-dried OFSP powder produced from the optimized conditions showed hexagonal in shapes, irregular in arrangement and compact. The OFSP powder had lower relative crystallinity (34.7%). In conclusion, the optimized OFSP powder with highest β-carotene and desirable physiochemical properties was produced and it can effectively utilize in the food formulation products.