The start-up current control of the high-speed brushless DC (HS-BLDC) motor is a challenging research topic. To effectively control the start-up current of the sensorless HS-BLDC motor, an adaptive control method is proposed based on the adaptive neural network (ANN) inverse system and the two degrees of freedom (2-DOF) internal model controller (IMC). The HS-BLDC motor is identified by the online least squares support vector machine (OLS-SVM) algorithm to regulate the ANN inverse controller parameters in real time. A pseudo linear system is developed by introducing the constructed real-time inverse system into the original HS-BLDC motor system. Based on the characteristics of the pseudo linear system, an extra closed-loop feedback control strategy based on the 2-DOF IMC is proposed to improve the transient response performance and enhance the stability of the control system. The simulation and experimental results show that the proposed control method is effective and perfect start-up current tracking performance is achieved.