Cystic echinococcosis (CE) /hydatid cyst is one of the most important helminthic diseases in the world. The treatment of hydatid cyst ranges from surgical intervention to chemotherapy, although the efficacy of chemotherapy is still unclear. Postoperative complication which results from the spillage of cysts during surgical operation is one of the most important concerns in surgical treatment of hydatid cyst. The aim of the current study was to solidify the hydatid cyst fluid (HCF) with an injectable and thermo sensitive chitosan (CS) /carboxymethyl cellulose (CMC) /b-glycerol phosphate (BGP) hydrogel for effective control of spillage during the aspiration of hydatid cysts. Fourier-transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), water uptake, rheological analysis, and Alamar Blue cytotoxicity assay were employed to characterize the hydrogel. A five level with three times replication at the central point using a central composite design (CCD), which is a response surface methodology (RSM), was used to optimize the experimental conditions. Assessment of the produced hydrogel showed that the intermolecular interactions of amino groups of chitosan and hydrogen groups of CMC were correctively established and appreciable swelling with a good strength was obtained. Hydrogels morphology had a porous structure. Rheological analysis showed that CS/CMC/BGP blends had a phase transition (32–35°C) of sol–gel close to the body temperature. Alamar Blue cytotoxicity assay showed that CS (1.75%) /CMC (1.4%) /BGP (2.9%) had IC50 values of 0.598, 0.235 and 0.138 (mg/mL) for 24, 48 and 72 h, which indicated that the produced polymer solution had no significant cytotoxic effect for human fibroblast cell line. In vitro injection of the polymer solution of CS/CMC/BGP with CS/CMC ratio of 1.75/1.4 was done on HCF (1 mL polymer solution to 3 mL of HCF) at 37°C with a final concentration of 2.9% for BGP resulting in solidification of HCF in less than 45 min.