To explore the clinical characteristics of immune-related thyroid dysfunction (TD) and its correlation with prognosis. By collecting the clinical data of 116 patients with advanced esophageal squamous cell carcinoma (ESCC) who received programmed death receptor-1 (PD-1) inhibitor treatment, we analyzed the clinical characteristics of immune-related TD and its influencing factors and compared the prognostic differences among patients in different groups. Immune-related TD occurred in 45 (38.8%) patients after PD-1 inhibitor treatment, and the median time to its occurrence was 11.3 weeks. The toxicity of immune-related TD was grade 1 or grade 2 and only required symptomatic treatment. Female patients, as well as those with an Eastern Cooperative Oncology Group Performance Status less than equal to 1, no lymph node metastasis, no history of drinking, and high baseline thyroid-stimulating hormone levels, were likely to develop immune-related TD. Compared with the patients in the group without immune-related TD [TD(-)], the median progression-free survival (mPFS) and median overall survival (mOS) of the patients in the immune-related TD [TD(+)] group were significantly prolonged (mPFS: 12.6 vs. 6.5 months, P = 0.001
mOS: 20.2 vs. 11.2 months, P <
0.001). Further subgroup analysis showed that compared with the patients in the group without immune-related overt TD (Overt_TD), the patients in the Overt_TD group had a longer PFS (mPFS: 12.4 vs. 7.3 months, P = 0.015) and OS (mOS: 20.2 vs. 12.2 months, P = 0.001). The 60-, 90-, and 120-day landmark analysis further confirmed that immune-related TD was significantly associated with the improvement of PFS and OS. Multivariate Cox regression analysis indicated that immune-related TD was an independent prognostic factor for PFS (P = 0.015) and OS (P = 0.004). Immune-related TD is a very common immune-related adverse event. It is safe and manageable and has potential prognostic value for patients with advanced ESCC treated with PD-1 inhibitors.