Zinc alloys have emerged as promising materials for bone regeneration due to their moderate biodegradation rates. However, the blast release of Zn2+ from Zn alloy substrates affects cell behaviors and the subsequent osseointegration quality, retarding their early service performance. To address this issue, extracellular matrix-like hydroxyapatite (HA) nanorods were prepared on Zn-1Ca (ZN) by a combined hydrothermal treatment (HT). HA nanoclusters nucleate on the presetting ZnO layer and grow into nanorods with prolonged HT. HA nanorods protect the ZN substrate from serious corrosion and the corrosion rate is reduced by dozens of times compared with the bare ZN, resulting in a significantly decreased release of Zn2+ ions. The synergistic effect of HA nanorods and appropriate Zn2+ endow ZN implants with obviously improved behaviors of osteoblasts and endothelial cells (e.g. adhesion, proliferation and differentiation) in vitro and new bone formation in vivo. Our work opens up a promising avenue for Zn-based alloys to improve bone regeneration in clinics.