With the combination of molecular simulation and relevant experiments, the efficient Bronsted-Lewis acidic ionic liquid (IL) was designed and synthesized for biodiesel production from soapberry oil. In molecular simulation, 4-methylthiazole (MT) is proved to be the best matrix for IL preparation via electrostatic potential analysis and proton affinity analysis, and it also is verified by experiments. In orthogonal experiment, the relationship in catalytic activity between Bronsted-Lewis acidic IL and corresponding materials (Bronsted acidic IL and metal chloride) was revealed. Meanwhile, [Ps-MTH] [CF3SO3] and FeCl3 are verified as the best materials for preparation of Bronsted-Lewis acidic IL, and [Ps-MTH] [CF3SO3]-FeCl3 (x = 0.65) is determined as the most efficient catalyst in the end. The Lewis acidity, Bronsted acidity and interaction of [Ps-MTH] [CF3SO3] and FeCl3 in [Ps-MTH] [CF3SO3]-FeCl3 (x = 0.65) were characterized by FT-IR. And the catalytic mechanism of transesterification catalyzed by prepared IL was clarified. In order to maximize the biodiesel yield, optimization of process variables was conducted using Box-Behnken response surface methodology. The 97.04% of high biodiesel yield is obtained under the optimum conditions: reaction temperature was 127 degrees C, molar ratio (methanol to soapberry oil) was 27.96:1, catalyst amount was 3.06 mmol and reaction time was 8 h. Furthermore, [Ps-MTH] [CF3SO3]-FeCl3(x = 0.65) presents good catalytic activity in different transesterification for biodiesel production. And its catalytic activity decreases from 97.04% to 93.59% after being used for 5 times, which reflects good reusability. The main properties of soapberry biodiesel were also measured and compared to the ASTM D6751 standard.