A layout structure of an ESD protection semiconductor device includes a substrate, a first doped region, a pair of second doped regions, a pair of third doped regions, at least a first gate structure formed within the first doped region, and a drain region and a first source region formed at two sides of the first gate structure. The substrate, the first doped region and the third doped regions include a first conductivity type. The second doped regions, the drain region and the first source region include a second conductivity type complementary to the first conductivity type. The first doped region includes a pair of lateral portions and a pair of vertical portions. The pair of second doped regions is formed under the pair of lateral portions, and the pair of third doped regions is formed under the pair of vertical portions.