Magnetic nanoparticles (MNPs) have attracted significant interest thanks to their small size, supermagnetism and low toxicity. However, with their large surface area, MNPs tend to aggregate and are sensitive to oxidation. To overcome this drawback, one of the solutions is surface modification of MNPs using many kinds of coating materials. Among them, carboxymethyl dextran is commonly used due to its high density of carboxymethyl groups which provide negative charge for stabilizing the ferrofluid and are available for attaching bioactive molecules. In this study we describe new methods of using microwave in carboxymethylation and Fe3O4 MNPs synthesis. Curcumin was then loaded on the coated MNPs to form a drug delivery system. The systems then were characterized and tested for cytotoxicity on cancer cells. Results show that our drug delivery system had small size of about 15–20 nm and saturation magnetization of 48.6 emu g−1. Moreover, our system had strong anticancer effect against Hep-G2 and LU-1 cancer cell lines. Therefore, it can be a promising candidate for a novel anticancer treatment.