ABSTRACT This investigation aims to develop a stimuli‐responsive nanocarrier to enhance the therapeutic efficiency of siRNA. Poly(ethylene imine) (PEI) and 3‐[(4‐Methylphenyl)thio]propionic acid (MPPA) were used to develop ion pair self‐assembly (IPSAM). This ion pair exhibited an upper critical solution temperature (UCST) behavior, and the UCST decreased when the H 2 O 2 concentration increased. The FT‐IR spectrum and 1 H‐NMR were studied in this study to verify the interaction between PEI and MPPA. IPSAM was found to be circular in TEM images, and the zeta potential of all IPSAM ratios showed positive results because IPSAM was likely affected by PEI. Therefore, the negatively charged siRNA can be loaded into IPSAM through the electrostatic interaction. At a temperature above UCST, IPSAM could be disassembled and release siRNA. In the oxidation, the sulfide bond of MPPA could be oxidized by H 2 O 2 to sulfone and sulfoxide. The UCST of the ion pair decreased, and IPSAM broke down, resulting in the promoted release. Pt nanoparticles were synthesized using the in situ method and contained in IPSAM. Under NIR irradiation, IPSAM can release the payloads due to heat generation and disassemble IPSAM. Moreover, siRNA loaded into IPSAM exhibited excellent cellular uptake and low cytotoxicity to C2C12 cells in vitro.