The aim of this article is to use zeolitic imidazolate framework-8 (ZIF-8) metal-organic frameworks (MOFs) as drug delivery system for lidocaine, a local anesthetic with recently discovered antitumoral effects, in particular for the early-stage treatment of breast cancer. A previously optimized ZIF-8 synthetic method is employed, and the prepared material is deeply characterized with X-ray powder diffraction (XRPD), surface area analysis, scanning electron microscopy (SEM), and thermogravimetric analysis (TGA). After confirming the successful synthetic outcomes, a tailored loading procedure is developed to incorporate lidocaine within the ZIF-8 pores. The effectiveness of this loading process is verified using UV-Vis spectroscopy and TGA, while SEM and attenuated total reflectance-mid infrared spectroscopy further confirms the presence of lidocaine within the MOF pores. Afterwards, the pH-responsive drug release by dialyzing the lidocaine@ZIF-8 sample is tested either at physiological or at weakly acid pH values by UV spectroscopy on the dialysis solutions. Finally, the MDA-MB-231 breast cancer cells viability of lidocaine@ZIF-8 system is tested and compared with the free drug and the MOF alone, confirming its significant capabilities in the reduction of cells viability.