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Bone fractures and defects are a major health issue and have reportedly affected over 455 million individuals globally to date. Bone tissue engineering has gained great success in bone defect repair and bone reconstruction based on the use of nano-hydroxyapatite (nHA) or collagen (COL). Both nHA and COL exhibit osteogenic induction capacity to support bone tissue regeneration; however, the former suffers from poor flexibility and the latter lacks mechanical strength. Biological scaffolds created by combining nHA and COL (nHA/COL) can overcome the drawbacks imposed by individual materials and, therefore, have become widely applied in tissue engineering. The composite scaffolds can further promote tissue reconstruction by allowing the loading of various growth factors. Naringin (NG) is a natural flavonoid. Its molecular weight is 580.53 Da, lower than that of many growth factors, and it causes minimal immune responses when being introduced in vivo. In addition, naringin is safe, non-toxic, inexpensive to produce, and has superior bio-properties. In this study, we introduced NG into a nHA/COL scaffold (NG/nHA/COL) and exploited the potentials of the NG/nHA/COL scaffold in enhancing bone tissue regeneration. NG/nHA/COL scaffolds were fabricated by firstly combining nHA and collagen at different compositional ratios, followed by NG encapsulation. NG release tests showed that the scaffold with a nHA/COL mass ratio of 7:3 exhibited the optimal property. The in vitro cell study showed the desirable biocompatibility of the NG/nHA/COL scaffold, and its effective promotion for the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs), as proved by an increased alkaline phosphatase (ALP) activity, the formation of more calcium nodules, and a higher expression of osteogenic-related genes involving Osteocalcin (OCN), BMP-2, and Osteopontin (OPN), compared with the control and nHA/COL groups. When administered into rats with skull defects, the NG/nHA/COL scaffold significantly promoted the reconstruction of bone tissues and the early repair of skull defects, indicating the great potential of NG/nHA/COL scaffolds in bone tissue engineering.