In this study, we propose the self-tuning interval type-2 fuzzy proportional derivative plus proportional integral (STIT2FPD+PI) controller, which consists of two fuzzy processors. The first is the IT2FPD+PI controller, which is a parallel combination of the IT2FPD controller and the IT2FPI controller and it is used as the main controller. The second is the tuning mechanism, which is a type-1 fuzzy logic system (T1FLS) that used as parameters tuning. The tuning mechanism generates the updating factors that update the output scaling factors (SFs), the output membership functions (MFs) and the degree of uncertainty for the input MFs. The proposed STIT2FPD+PI controller is implemented practically based on a microcontroller for controlling the overhead crane system. The test is established using the hardware-in-the-loop (HIL) simulation. The practical results show that the proposed STIT2FPD+PI controller improves significantly the performance over a wide range of system uncertainties.