Prestressed concrete pipe piles (PC pipe piles) are often used to deal with various complex geological conditions due to their advantages of reliable pile quality, strong adaptability and economical cost. Taking the actual project of a science and technology industrial park in Henan Province as an example, vsing the finite element software ABAQUS and CEL method to construct a three-dimensional numerical model of soil body (Euler body) and pile foundation (solid), and considering the difference in the length and diameter of PC pipe piles and the different sinking speed of the same pile size in the actual pile sinking process, the response law of the stress and settlement of the weak soil interlayer around the pile and the pile sinking time of the pile foundation are compared and analyzed. The results show that the changes of stress and settlement in weak soil interlayer are consistent with the different sinking speeds of the same pile size. When the pile diameter is the same, the stress and settlement of the same soil body unit in the weak soil interlayer will increase with the increase of pile length. When the pile length is the same, the stress and settlement of the soil body unit of the weak soil interlayer at the same distance from the outer surface of the pile will increase with the increase of pile diameter. Through comprehensive consideration, the size of the prestressed concrete pile in line with the actual project is given. The research results can provide an important theoretical basis for the construction of key technologies of prestressed concrete pipe piles under the site of weak soil interlayer.