In karst terrain, base rock surface is undulate and space of karst cavity is various. When pile foundation is used in karst, it is necessary to consider the stability issues of pile foundation. Based on the interrelation of pile and surface characteristics of the base rock and karst cavity position, the stability issues of pile foundation in karst may be divided into two kinds. One is the stability issue of the cavity roof between the bottom of pile and karst cavity under the loading. The other is the stability of covered karst free-body when the bottom of pile is located near the free-plane. Through using the three dimension finite element method (3D FEM), the computer simulation and the multiple linear regression method, this paper analyzes the two kinds of stability issue and discusses factors of the stability. The equation of the critical value of safe roof thickness is given, and the size of karst cavity and the design loading of pile are also included. The equation of the critical loading of pile located near the free-plane is given, and the thickness of soil above, the friction coefficient, obliquity and highness of structure plane and the obliquity of free-plane are also included. Engineers can use these equations to design pile foundation in karst conveniently. These equations are validated by using many engineering examples in China and the results indicate that these equations are applicable.