A gelatin based pH responsive composite hydrogel has been synthesised by grafting β-cyclodextrin (β-CD) to gelatin (Gel) and crosslinking with oxidised dextran (OX-Dex). This pH sensitive β-CD grafted Gel crosslinked with OX-Dex (β-CD-g-Gel/OX-Dex) or composite hydrogel (CHG) was used to investigate the colon delivery of 5-fluorouracil (5-FLU), an anti cancer drug. Fourier Transform Infrared Spectroscopy (FTIR) was used to confirm the grafting of β-CD, crosslinking and drug encapsulation. Powder X-ray diffraction (PXRD) reveals the amorphous character of CHG. Factors affecting the swelling were thoroughly studied. The grafting of β-CD enhanced the drug encapsulation capacity. Release data were fitted to empirical equations to understand the nature of the drug release profiles. The drug release profile followed the Higuchi model. Degradation and swelling of the hydrogel were found to contribute to the release of drug. Release profiles of 5-FLU were studied both at gastric pH (1.2) and at intestinal pH (7.4); the results showed that release is very low at pH 1.2 and high at pH 7.4. An in vitro cytotoxicity study was carried out on human colon cancer cells; the results showed that drug loaded β-CD-g-Gel/OX-Dex (CHG) showed enhanced cell inhibition compared to the drug alone. Results of the present investigation exemplify the potential of this novel pH switchable composite hydrogel for the controlled and targeted delivery of the anti cancer drug 5-FLU.