The purpose of this study was the investigation of the potential of MIL-101(Fe) for load and sustained release of curcumin (CCM), as an anticancer drug, with pH stimulus. The reasons for choosing this type of metal-organic framework (MOF) are its high surface area, acceptable stability in a water medium, and its biocompatible components (iron and terephthalic acid) with low toxicity to normal cells. The obtained results from UV-vis analysis confirmed that this MOF is a smart carrier with a higher release rate in acidic pH (pH 5), which is a condition similar to that in cancer cells, than that at pH 7.4 (in normal cells). Therefore, this MOF is a pH-stimulus-controlled release carrier with 56.3% drug loading content and sustained drug release over 22 days. In order to evaluate the cell viability after treatment with free CCM, MIL-101(Fe), and MIL-101(Fe)@CCM, the cytotoxicity investigation using MTT assays was performed against HeLa and HEK 293 cell lines up to 48 h. Obtained results showed that MIL-101(Fe)@CCM exhibited more cell growth inhibition effect on HeLa cells in comparison with HEK 293. One of the reasons for the high loading and sustained release of CCM was surface adsorption of this drug and its interactions with open metal sites in MIL-101(Fe). In the end, the kinetic models of drug release were evaluated, and the obtained results showed that in this case diffusion is the main driving force for the drug release process.