To investigate the influence of underlying karst on pile foundation’s bearing capacity, orthogonal tests were simulated in FLAC3D under different karst conditions—five different thicknesses and widths of karst roof, five different heights of karst cave, and three different types of surrounding rock—based on field static load test. Results demonstrated that given the same other circumstances, the bearing capacity of pile foundation is directly proportional to the thickness of cave roof and strength of surrounding rocks, inversely proportional to the width of cave roof, and has no direct relation with cave height. Karst caves and other weak substratum affects the upper pile foundation within a depth maximum to three times pile diameter. Further increasing the thickness of cave roof has little effect on improving the ultimate bearing capacity of pile foundation. Cave size has little effect on pile’s bearing capacity when cave size is close to pile diameter(L≤2D), but reduces the ultimate bearing capacity evidently when cave size continues to grow. The bearing capacity grows apparently with the increase of rock mass strength when the strength is below 11.5 MPa, but the growth is not obvious when the strength is over 11.5 MPa.