Despite their considerable potential, using in situ injectable hydrogels for drug delivery has some associated drawbacks. The ratio of precursor to reaction required for gelation is a relatively fine balance, and low strength makes the gel prone to plastic deformation. To improve gel strength, poly (thiolated chitosan-co-alkylated -cyclodextrin) [poly (CS-SH-co-Alkynyl--CD)] hydrogels with high cross-linking density were first obtained by click chemistry. Chitosan and cyclodextrins are derived from natural polymers and can be modified with mercapto and alkynyl groups, respectively, to achieve gels with high cross-linking density. The physical properties of the gels were optimized by adjusting the mass ratio of thiolated chitosan and alkylated -cyclodextrins. Experiments revealed that the in situ hydrogels exhibit good mechanical properties. Furthermore, the specific binding and controlled release of a model drug, bendamustine hydrochloride, were studied using in situ gels as carriers. The in situ hydrogel also exhibited excellent degradation. In situ mutual cross-linking poly (CS-SH-co-Alkynyl--CD) hydrogels are therefore an efficient drug delivery method requiring minimal invasive surgery, and have attractive application prospects in the treatment of solid tumors.