AIM: To evaluate the relationship between monocyte to high-density lipoprotein cholesterol ratio (MHR) and the disease activity of thyroid-associated ophthalmopathy (TAO). METHODS: A total of 87 patients were classified into two groups based on clinical activity score (CAS) scoring criteria: high CAS group (n=62, the CAS score was ≥3); low CAS group (n=25, the CAS score was <3). In addition, a group of healthy people (n=114) were included to compared the MHR. Proptosis, MHR, average signal intensity ratio (SIR), average lacrimal gland (LG)-SIR, average extraocular muscles (EOM) area from 87 patients with TAO were calculated in magnetic resonance imaging (MRI), and compared between these two groups. Correlation testing was utilized to evaluate the association of parameters among the clinical variables. RESULTS: Patients in high CAS group had a higher proptosis (P=0.041) and MHR (P=0.048). Compared to the healthy group, the MHR in the TAO group was higher (P=0.001). Correlation testing declared that CAS score was strongly associated with proptosis and average SIR, and MHR was positively associated with CAS score, average SIR, and average LG-SIR. The area under the receiver operating characteristic curve (AUC) of MHR was 0.6755. CONCLUSION: MHR, a novel inflammatory biomarker, has a significant association with CAS score and MRI imaging (average SIR and LG-SIR) and it can be a new promising predictor during the active phase of TAO.