Giant non-functioning pituitary adenomas (NFPAs) often extend into or compress critical structures, such as the optic nerves, brainstem, and cavernous sinus, frequently making complete surgical resection difficult or unfeasible and posing significant therapeutic challenges. Radiotherapy (RT) is crucial for unresectable or residual disease, yet conventional techniques may struggle to deliver adequate doses while sparing organs at risk (OARs). Proton beam therapy (PBT), particularly intensity-modulated proton therapy (IMPT), offers potential dosimetric advantages, such as superior conformity and OAR sparing. This report presents an IMPT case for a giant, recurrent, unresectable NFPA and reviews the PBT literature, focusing on its advantages and role in NFPA management. A 49-year-old female presented with headache and progressive visual decline, approximately six years after her second surgery for a pituitary adenoma, which was first diagnosed in 2013. Contrast-enhanced magnetic resonance imaging (MRI) revealed a giant (>5 cm), unresectable, recurrent NFPA extending into the cavernous sinus and compressing the optic chiasm, brainstem, and right temporal lobe, and encasing the optic nerves and internal carotid arteries. Given the tumor's complex geometry and the patient's age, IMPT (54 Gy RBE (relative biological effectiveness)/30 fractions) was administered. MRI performed approximately 16 months post-IMPT showed significant tumor reduction and relief of brainstem and optic chiasm compression, indicating effective local control without acute high-grade toxicity. The physical properties of protons, characterized by the Bragg peak, allow for superior dose conformity and sparing of critical OARs. In this complex case, IMPT demonstrated excellent tumor control. This reduction in integral dose to healthy tissue theoretically lowers long-term risks, particularly the development of secondary malignant neoplasms (SMNs), making IMPT an advantageous modality for challenging NFPAs - especially in younger patients with long life expectancies. Further prospective studies are needed to clinically validate these long-term benefits and solidify IMPT's role in the treatment of pituitary adenomas.Copyright © 2025, Yan et al.