The drilling with pre-stressed concrete pile cased (DPC) pile was newly developed as engineering foundations, and engineers have accepted the designing method in practice. However, several key problems for ultimate shaft frictional resistance still need to be specifically investigated due to insufficient information in the literature. First, the pile-soil interface failure mode is unclear due to its multiple structural layers. Second, the grouting reinforcement mechanism needs to be specified. And last, the values of ultimate shaft frictional resistance need to be determined. This paper presents an experimental investigation on the physical mechanism and failure model on DPC pile-soil interface, which are limited thickness and three structural layers. For this purpose, a series of large-scale direct shear tests were performed. Fourteen large-scale direct shear tests on interfaces were carried out, including eight non-grouted DPC pile-soil interfaces and six grouted DPC pile-soil interfaces. The silt-clay and moderate dense sand were tested as the typical stratum around the DPC pile. The experimental results indicates the shear surface located on the interface between the grouting concrete and the boundary soil. Using the linear Mohr-Coulomb envelopes, the friction angles, and cohesion are obtained for the non-grouted DPC pile-soil interfaces and the grouted DPC pile-soil interfaces. Moreover, the ultimate shaft frictional resistance determined for the tested specimens are obtained. Values of ultimate shaft frictional resistance determined using grouted DPC pile-soil interfaces are compared with those determined non-grouted DPC pile-soil interfaces. Finally, the grouting reinforcement mechanism on DPC pile-soil interface was specified. The findings of this study should lead to a better understanding of the designing and construction of DPC pile at in-situ sites.