Bone contains an organic matrix composed of aligned collagen fibers embedded with nanosized inorganic hydroxyapatite (HAp). Many efforts are being made to mimic the natural mineralization process and create artificial bone scaffolds that show elaborate morphologies, excellent mechanical properties, and vital biological functions. This study reports a newly discovered function of lignin mediating the formation of human bone-like HAp. Lignin is the second most abundant organic material in nature, and it exhibits many attractive properties for medical applications, such as high durability, stability, antioxidant and antibacterial activities, and biocompatibility. Numerous phenolic and aliphatic hydroxyl moieties exist in the side chains of lignin, which donate adequate reactive sites for chelation with Ca2+ and the subsequent nucleation of HAp through coprecipitation of Ca2+ and PO43-. The growth of HAp crystals was facilitated by simple incubation of the electrospun lignin/polycaprolactone (PCL) matrix in a simulated body fluid. Multiple analyses revealed that HAp crystals were structurally and mechanically similar to the native bone. Furthermore, the mineralized lignin/PCL nanofibrous films facilitated efficient adhesion and proliferation of osteoblasts by directing filopodial extension. Our results underpin the expectations for this lignin-based biomaterial in future biointerfaces and hard-tissue engineering.