Thermosensitive hydrogels are of great potential in in situ implantation for long-term controlled drug release. The present article reviewed the recent research progress in the preparation of thermosensitive hydrogel and the drug delivery system, the body response to and the degradation of the hydrogel, as well as the drug release form the hydrogel. The challenges of implant drug delivery based on thermosensitive hydrogel were presented and the solutions were discussed. The major handicaps in controlled drug delivery of the thermosensitive hydrogel include the flexible network with high water content and low mechanical strength, inducing the body inflammatory responses and invaded by the tissue after implantation, and the individual differences in the degradation and evolution of the network. Many researches developed various approaches to overcome these handicaps. The body inflammatory responses and tissue invading can be mitigated by either improving the hydrophilicity and reducing the positive charge of the hydrogel or incorporation with the anti-inflammatory peptides. The mechanical strength might be promoted by cross-linking, blending hydrophilic polymer in to the hydrogel, or preparing the interpenetrating polymer network, so that the network and water can be maintained for longer period. Further approaches to improve the controlled drug delivery involve building drug diffusion barrier on the hydrogel surface, enhancing the interaction between the drug and the polymer in hydrogel, and the combination hydrogel with drug-loaded micro/nanoparticles.