This paper proposes a cascaded control structure and a method of practical application for attitude control of a multi-rotor Unmanned aerial vehicle (UAV). The cascade control, which has tighter control capability than a single-loop control, is rarely used in attitude control of a multi-rotor UAV due to the input-output relation, which is no longer simply a set-point to Euler angle response transfer function of a single-loop PID control, but there are multiply measured signals and interactive control loops that increase the complexity of evaluation in conventional way of design. However, it is proposed in this research a method that can optimize a cascade control with a primary and secondary loops and a PID controller for each loop. An investigation of currently available PID-tuning methods lead to selection of the Simple internal model control (SIMC) method, which is based on the Internal model control (IMC) and direct-synthesis method. Through the analysis and experiments, this research proposes a systematic procedure to implement a cascaded attitude controller, which includes the flight test, system identification and SIMC-based PID-tuning. The proposed method was validated successfully from multiple applications where the application to roll axis lead to a PID-PID cascade control, but the application to yaw axis lead to that of PID-PI.