The objective of the present study was to prepare canola oil based vitamin E nanoemulsions by using food grade mixed surfactants (Tween:80 and lecithin; 3:1) to replace some concentration of nonionic surfactants (Tween 80) with natural surfactant (soya lecithin) and to optimize their preparation conditions. RBD (Refined, Bleached and Deodorized) canola oil and vitamin E acetate were used in water/vitamin E/oil/surfactant system due to their nutritional benefits and oxidative stability, respectively. Response surface methodology (RSM) was used to optimize the preparation conditions. The effects of homogenization pressure (75–155 MPa), oil concentrations (4–12% w/w), surfactant concentrations (3–11% w/w) and vitamin E acetate contents (0.4–1.2% w/w) on the particle size and emulsion stability were studied. RSM analysis has shown that the experimental data could be fitted well into second-order polynomial model with the coefficient of determinations of 0.9464 and 0.9278 for particle size and emulsion stability, respectively. The optimum values of independent variables were 135 MPa homogenization pressure, 6.18% oil contents, 6.39% surfactant concentration and 1% vitamin E acetate concentration. The optimized response values for particle size and emulsion stability were 150.10 nm and 0.338, respectively. Whereas, the experimental values for particle size and nanoemulsion stability were 156.13 ± 2.3 nm and 0.328 ± 0.015, respectively.