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This paper presents an intelligent motion controller for four-wheeled holonomic mobile robots with four driving omnidirectional wheels equally spaced at 90 degrees from one another by using field-programmable gate array (FPGA)-based artificial immune system (AIS) algorithm. Both the nature-inspired AIS computational approach and motion controller are implemented in one FPGA chip to address the optimal control problem of real-world mobile robotics application. The proposed FPGA-based AIS method takes the advantages of artificial intelligence and FPGA technology by using system-on-a-programmable chip (SoPC) methodology. Experimental results are conducted to show the effectiveness and merit of the proposed FPGA-based AIS intelligent motion controller for four-wheeled omnidirectional mobile robots. This FPGA-based AIS autotuning intelligent controller outperforms the conventional nonoptimal controllers, the genetic algorithm (GA) controller, and the particle swarm optimization (PSO) controller.