<p>Prosthetic rehabilitation remains the predominant strategy for the reconstruction of maxillary defects. However, conventional impression techniques are often cumbersome and uncomfortable for patients, while the limited precision of medical-grade silicone 3D processing presents additional challenges to achieving optimal prosthetic outcomes. This technical note introduces a novel digital workflow for the design and fabrication of split negative molds for obturator prostheses in post-maxillectomy patients, aiming to address both the discomfort associated with traditional impression-taking and the inaccuracies commonly encountered in prosthesis manufacturing. The proposed protocol integrates spiral computed tomography (CT), reverse engineering, and three-dimensional (3D) printing technologies. CT-derived 3D reconstructions were utilized to accurately capture the morphological characteristics of both soft and hard tissues at the defect site. Defect margin delineation and obturator design were performed using Geomagic Studio 2013 software. Subsequently, a stereolithography apparatus (SLA) was employed to fabricate a split negative mold featuring interlocking alignment structures, which facilitated the production of a hollow silicone obturator. This fully digital approach effectively overcomes several limitations inherent in conventional methods, including patient discomfort during impression-taking and the imprecision associated with traditional silicone prosthesis fabrication. The resulting prosthesis demonstrated favorable clinical outcomes, significantly enhancing patient comfort and restoring essential oral functions such as speech, swallowing, and mastication. Importantly, this technique offers particular advantages for patients with limited mouth opening following maxillectomy.</p>