Although flurbiprofen (FB), as one of non-steroidal anti-inflammatory drugs, has various pharmacological applications, it shows low dermal bioavailability due to its low water solubility. To overcome this solubility problem, FB nanosuspensions were developed and the effects of stabilizers were investigated with regard to critical quality attributes. While PVP K30 and HPMC 3 cps were used as non-ionic polymeric stabilizer, Tween 80 and Plantacare 2000 (PL) were used as non-ionic surfactants. The influence of these types of stabilizers and their different ratios were tested. The selected formulations according to results of experimental design were also characterized by SEM, FTIR, XRPD, DSC, and the stability studies were performed. According to results of characterization studies, PL was selected as the appropriate stabilizer. The determined nanosuspension stabilized with PL had the nanosized, spherical, and homogenous dispersed particles. There is no polymorphic change on the crystalline state of FB while producing nanosuspension stabilized with PL. It also retained its stability compared with PVP stabilized nanosuspensions for one month. It was concluded that the design of experimental approach is a useful tool to determine the effect of stabilizer on quality attributes of nanosuspensions and to select the optimum type and ratio of stabilizer for obtaining more stable nanosuspensions.