The study involves preparing starch nanocrystals by acid hydrolysis of starch and to produce a new chemical crosslinking starch nanocrystals/gum Arabic blend in the presence of potassium persulfate (K 2 S 2 O 8 ) as an initiator. The new materials were characterized and its potential utilization in controlled drug delivery and cancer therapy were investigated. Crosslinked starch nanocrystals/gum Arabic blends were loaded with hydroxyurea drug. The properties of starch nanocrystal was characterized by x-ray diffraction (XRD), atomic force microscopy (AFM), Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM). The starch nanocrystal /gum Arabic blends were analyzed in vitro drug release studies by using UV-vis spectroscopy. The swelling test and MTT assay were also investigated. The drug release and the swelling test were monitored at pH7.4 and pH4. XRD result showed that starch nanocrystal was the crystalline A-type. Starch nanocrystal showed a high degree of crystallinity compared with the native starch. The experimental results proved that starch nanocrystal/gum Arabic/hydroxyurea blends reduced the swell ability of blends which lead to slow release of hydroxyurea, and the rate of hydroxyurea release was significantly higher at pH7.4 than pH4, at constant incubation time. The swelling ratio and drug release were decreased by using starch nanocrystal/hydroxyurea while the swelling ratio and drug release using starch nanocrystal/gum Arabic/hydroxyurea blend were lowest. The results of vitro cytotoxicity study showed that the 100 μg ml −1 hydroxyurea concentration killed ∼39% colorectal cancer cells while ∼27% of cells were killed by using starch nanocrystal/gum Arabic/hydroxyurea blends at the same concentration for 24 h of incubation. It was concluded that the hydroxyurea loaded starch nanocrystal/gum Arabic blend enhanced the controlled drug release system thereby, revealing a novelsvehicle for cancer therapy.