The application range of hydrogels can be greatly widened by improving their mechanical properties. It is still a great challenge to develop hydrogels with good mechanical properties, reliable self-healing properties and remolding ability at the same time. Inspired by biological soft tissue with excellent mechanical properties and self-healing properties, here, a facile method to fabricate poly (styrene-acrylic acid) (P(S-AA)) core-shell nanoparticles with plenty of carboxyl groups on their surface, and their enhancement to hydrophobic association hydrogels was reported. Under stress, the dynamic physical bonds including hydrogen bonding between polymer chains and P(S-AA) core-shell nanoparticles (NPs), and entanglement of hydrophobic chains were destroyed to effectively dissipate energy, and uniform hydrogel network leads to smooth stress-transfer, which makes the core-shell nanoparticles composite hydrophobic association hydrogels (MHA gels) excellent mechanical properties, such as excellent mechanical properties, toughness and ductility, and good self-healing properties as well. These features make the MHA gels have great potential in biomedical applications such as tissue engineering, articular cartilage and artificial skin.