Head and neck squamous cell carcinomas (HNSCC) are aggressive malignancies with poor prognosis and limited therapeutic options. Electrochemotherapy (ECT), combining short electric pulses with chemotherapeutic agents to enhance intracellular drug uptake, has shown clinical potential but still requires physiologically relevant in vitro models for protocol optimization and mechanistic studies. Here, we present a pilot study introducing a 3D bioprinted in vitro HNSCC model specifically designed for electroporation testing. Structures were fabricated using a composite hydrogel of 8% sodium alginate and 4% gelatin (w/w), crosslinked with CaCl₂ at 0.5%, 1%, and 2% to modulate mechanical properties. Uniaxial compression testing confirmed elastic moduli spanning the physiological tumor stiffness range, with the 1% CaCl₂ formulation providing optimal mechanical and handling characteristics (42.96 ± 19.89 kPa). Hypopharyngeal carcinoma FaDu cells (5×10⁶/mL) embedded in three-layer structures (thickness: 1.05 mm) maintained 75–80% viability over 21 days and formed tumor-like spheroids (mean diameter: 303 ± 113 µm), reflecting native tumor architecture. Electroporation with 8 pulses at 200 V for 100 µs efficiently permeabilized the membrane without additional cytotoxicity, as evidenced by propidium iodide internalization. PD-L1 expression was preserved and upregulated in 3D spheroids compared to 2D controls, supporting the platform’s relevance for immuno-oncology studies. Compared to other 3D HNSCC models, our system integrates mechanical tuning, electroporation compatibility, and immune-related biomarker expression, enabling functional validation of electric-field–mediated intracellular delivery. This proof-of-concept platform demonstrates structural fidelity, long-term cell viability, and high reproducibility, offering a scalable, human-relevant tool for preclinical optimization of ECT and other electrically based therapies, bridging the gap between conventional 2D cultures and complex in vivo models.