The invention provides a PCB layout design method reducing differential crosstalk. When a chip differential pin bonding pan and a differential pair perform coupling layout, chip pins and the differential pair are in opposite coupling polarity, and crosstalk noises correspondingly generated by the chip pins and the differential pair are in opposite polarity, so that when noise signals are superpositioned, due to the opposite amplitude polarity, most of noise energy is bound to offset due to mutual superposition, and further crosstalk noise can be effectively reduced. Compared with the prior art, the PCB layout design method reduces signal crosstalk by optimizing the layout mode, thereby improving the product quality and effectively reducing the crosstalk influence due to high-density interconnection of high-frequency signals. Meanwhile, the PCB layout design method reducing the differential crosstalk has the advantages of being reasonable in design, simple in structure, convenient to use and the like, thereby obtaining high usage values.