Anterior cruciate ligament (ACL) injury is one of the most common injuries in sports, and ACL reconstruction with an artificial ligament is a good treatment for quick recovery. However, current artificial ligaments made of polyethylene terephthalate (PET) are still associated with some problems due to the hydrophobic nature and low biological induction activity of PET. Many efforts have been used to improve the biocompatibility of PET in recent years, and our previous work has shown that surface modification is an effective strategy. Here, a hydroxypropylcellulose (HPC) coating was applied on the surface of a PET artificial ligament order to improve its biocompatibility. The effects of the HPC coating on PET artificial ligament graft-bone healing was investigated in vitro using bone marrow stromal cells (BMSCs), fibroblasts and RSC-364 cells as well as in vivo in a beagle dog model of ACL reconstruction. HPC was coated successfully on the PET and significantly promoted cell growth, adhesion and capability of osteogenic differentiation compared to the PET graft without HPC coating. In vivo, the HPC coating significantly enhanced ligament tissue regeneration. Moreover, the expression of some bone formation-and ligament tissue regeneration-contributing proteins and cell factors, such as COL1, BMP-7, COL3, OCN, RUNX2, TGF-β1 and VEGF, was higher on the HPC-coated PET artificial ligament than on the pure PET artificial ligament. In conclusion, HPC coating can significantly improve the cytocompatibility and graft-to-bone healing of a PET artificial ligament for ACL reconstruction.