Introduction <p>Head and neck cancer is a common malignancy, and its current treatments face major challenges, including recurrence, drug resistance, side effects, and high costs. Epigallocatechin gallate (EGCG) from green tea has anticancer properties, but its low stability and bioavailability limit its clinical use. These limitations may be addressed by nanocarrier-based delivery systems.</p> Methods <p>Five different sizes of sodium alginate (SA) nanoparticles (NPs) were synthesized, and EGCG was loaded into the selected particles. Characterizations of SA NPs with and without EGCG were conducted using dynamic light scattering (DLS), field emission scanning electron microscopy (FE-SEM), and Fourier transform infrared spectroscopy (FTIR). Furthermore, loading capacity, entrapment efficiency, and release profile of the EGCG-loaded NPs were evaluated. The cytotoxicity and cell viability were assessed (MTT and LDH) on TSCC-1 cancer cells. Moreover, cellular uptake, wound healing, colony formation, and apoptosis were also tested.</p> Results <p>The characterizations of NPs confirmed the successful synthesis of SA NPs. Two NP sizes (type 1 and type 4) were selected for EGCG loading, for which the drug release was around 39% for type 1 and 51% for type 4 NPs after 14&#xa0;days. The optimal cytotoxicity on cancer cells was observed at a concentration of 80&#xa0;µg/mL of NPs (type 1). A significant reduction in colony numbers was observed after treatment with these EGCG-loaded NPs compared to controls. Furthermore, the EGCG-loaded NPs could prevent cancer cell migration, with an increase in apoptosis levels in TSCC-1 cells treated with type 1 NPs (80&#xa0;µg/mL).</p> Conclusion <p>It was demonstrated that EGCG-loaded SA NPs effectively inhibit the proliferation and migration and induce apoptosis in head and neck cancer cells.</p> Graphical abstract <p></p>