A power supply system with line loss reduction supplies power to a load through a power line. The power supply system includes a step-up converter, a detection circuit, and a control unit. The control unit sets a terminal voltage required by the load, controls an output voltage of the step-up converter to be terminal voltage, and acquires an output current corresponding to the terminal voltage to be a present current by the detection circuit. The control unit controls the output voltage to be a modulated voltage, and acquires an output current corresponding to the modulated voltage to be a modulated current by the detection circuit. The control unit adjusts the output voltage to be a first predetermined voltage according to the terminal voltage, the present current, the modulated voltage, and the modulated current.