Hydroxyapatite (HAp) is coassembled with many organic molecular templates led by collagens in natural bone. In this study, it is presumed that small intestinal submucosa (SIS) with acetamide group chelates calcium ion and bacterial cellulose (BC) has strong intermolecular hydroxyl group and powerful attraction for calcium ion to initiate initial nucleation. Phosphate ions bind calcium ions to form seed crystal of calcium phosphate, which is further directionally grown under the mediation of the template structure and finally forms weakly crystalline HAp, providing an environment for the HAp formation. Besides, the samples are characterized by X‐ray diffraction, Fourier transform infrared, X‐ray photoelectron spectroscopy, scanning electron microscope, and transmission electron microscope to unveil the phase structure, composition, and morphology, and a growth mechanism is proposed. HAp is successfully synthesized on SIS–BC biomineralization template. The results show morphology of samples from sheet‐lamellar‐like to flower‐like or porous‐spheroid‐like from 1 day to 7 days. The plate‐like HAp rods are polycrystal with c‐axis orientation. Interestingly, the HAp/SIS‐BC composites have the least relative mass of HAp on mineralization and the content of HAp (57%) is very close to the human bone tissue in structure (about 60%). Finally, the HAp mineralized films show good biocompatibility through MC3T3‐E1cells test for the potential biomaterials.