The Electro-Static Discharge (ESD) is one of the most important reliability problems in an electronic product. For Universal Serial Bus (USB) is a hot insertion and removal interface, its components are easily subject to ESD damage. This paper focuses on the influence of the using of USB in plugging and/or unplugging impact arisen from ESD. Employing the off-chip protection technique and commercial protection products, the paper proposes an ESD Protection Strategy for USB (EPSU) to effectively enhance ESD robustness. The comparisons among these ESD protection designs are also discussed.