Biocompatible and pH-sensitive biodegradable hydroxyapatite with mesoporous nanoplates (HAp PNPs) have been developed for nanoscaled drug delivery applications. Herein, we report a novel carboxymethylcellulose calcium salt-templated hydrothermal technique for the synthesis of HAp PNPs. The field emission scanning electron microscopy (FESEM) analysis reveals that the as-prepared HAp PNPs consist of spindle-like structure with a length of 20 nm and an average diameter of 10 nm, giving rise to plate like nanostructures due to their uniform assembly. The obtained HAp PNPs shows higher specific surface area of 180 m2 g-1 with a pore size distribution in the range from 20 to 60 nm. Moreover, HAp PNPs is characterized and investigated as a drug nanocarrier using Methotrexate and Andrographolide as a model drug. The HAp PNPs show a relatively high Methotrexate loading capacity and sustained release at a pH of 4.4. In addition, HAp PNPs used for the pH-triggered release of electrostatically bound Andrographolide anticancer drug into A431 cell lines toward cancer therapy applications. The significance of this study confirms that HAp with porous structure enhances the drug loading capacity and is capable of pH-sensitive Andrographolide release with an acidic pH of 4.4 is higher comparing at the pH of 7.0 and 9.0. On the top of everything, the cytotoxicity studies confirms that the prepared samples posses superior biocompatibility. These results promise the distinctive properties of HAp PNPs can be used as tumor-targetingpH-sensitive drug nanocarrier for biomedical applications. © 2019 IOP Publishing Ltd.