Herein, we report the successful synthesis of a series of poly (N-isopropylacrylamide) (PNIPA)/layered double hydroxides (LDHs)/nano-hydroxyapatite (nano-HA) hydrogels via in-situ radical polymerization. The internal morphology, thermo sensitivity, rheological properties, swelling behavior and hemocompatibility of the PNIPA/LDHs/HA composite hydrogels were systematically investigated. Results show that the hydrogels had a reversible sol-gel transformation around 33 °C. Interactions between the positively charged LDHs and negatively charged nano-HA particles created a highly porous hydrogel network. The composite hydrogels exhibited excellent hemocompatibility, incredible mechanical toughness and reversible swelling/deswelling behavior. To our knowledge, this is the first reported study to use two types of inorganic nanoparticle with opposing charges as hydrogel crosslinking agents. Based on its properties, we expect this hydrogel has broad applications potential in tissue engineering, drug delivery and biosensor development.