Background Thyroid-associated ophthalmopathy (TAO), the most common orbital disease in adults, is an autoimmune disease of the orbital and periorbital tissues. Typical ocular symptoms of TAO include periorbital oedema, conjunctival congestion and oedema, eyelid retraction, exophthalmos, restrictive strabismus, etc. Hypercholesterolaemia is considered one of the modifiable risk factors of TAO. However, it is unclear whether lipid levels are related to TAO activity and severity and the intravenous glucocorticoids (GC) therapeutic effect. The study aims to evaluate the association between initial lipid and lipoprotein levels, the clinical features of TAO and the efficacy of intravenous methylprednisolone in patients with moderate-to-severe TAO, as well as to explore the oxidative stress-related mechanisms involved.Methods and analysis This real-world prospective cohort study will recruit 178 patients with moderate-to-severe TAO who receive two intravenous methylprednisolone regimens, respectively. The primary outcome is the improvement in the composite index at 3 months after baseline treatment, with secondary outcomes including other ocular features, changes in serological characteristics and major adverse events.Ethics and dissemination The study protocol was approved by the ethics committees of Xiangya Third Hospital of Central South University (Kuai241012) on 29 November 2024. The study will be conducted according to the guidelines of the Declaration of Helsinki. Participants will be informed of the purpose and content of the study and will complete a written informed consent form before being recruited. The findings will be published in peer-reviewed journals as well as in reports of relevant conferences.Trial registration number Chinese Clinical Trial Registry (ChiCTR2400094094). Registered on 17 December 2024.