During the process that implant materials are used for bone replacement, the cell responses to implant materials determine the long-term stability of bone replacement. The microstructure of implant materials is considered as a critical factor that influences the cell responses. Carbon/Carbon composites (C/C composites) are novel implant materials, but there are few reports on the effect of their microstructure, especially the carbon matrixes and holes, on cell behavior. In this paper, C/C composites with different carbon matrixes are prepared by chemical vapor infiltration and pressure impregnation carbonization technique, respectively. The structure of holes is analyzed. The cell responses to C/C composites with different carbon matrixes are evaluated with MG63 osteoblast-like cells. The morphologies of MG63 osteoblast-like cells on the surface of C/C composites, especially in the holes are assessed by scanning electron microscope, and cell proliferation behavior is evaluated by 3-[4, 5-dimethylthiozol-2-yl]-2, 5-diphenyltetrazolium bromide (MTT) assay.The results show that MG63 osteoblast-like cells have a lamellar morphology with similar sizes and spreading areas as well as the same proliferation behaviors for C/C composites with different carbon matrixes. Carbon matrix shows unapparent influence on the cell growth behavior. Besides, MG63 osteoblast-like cells have various interactions with the holes of C/C composites. The cells stride over the holes with 6-8 μm in size, and connect with each other or grow along the curvature wall of the holes with a size of 30-40 μm; the cells present three-dimensional morphologies inside the holes and display circular shapes along the ridge of the holes. Diverse cell-material interactions are found according to the size and position of the holes, which provides theoretical foundation for the microstructure design of clinical C/C composites.