ABSTRACTBackground. Thyroid ranks 10th among the causes of death. Treatment of thyroid cancer mostly involves surgery (total thyroidectomy, isthmolobectomy, or hemithyroidectomy with or without lymphadenectomy) followed by radioiodine ablation therapy. The goal of thyroid cancer treatment is not only to enhance survival but also to improve or maintain HRQoL (Health Associated Quality of Life). Assessment of HRQoL in patients with low-risk DTC in several studies proves that isthmolobectomy is better than total thyroidectomy.Methods. This study used an observational analytical design with a prospective cohort approach. The subjects of the study were patients with differentiated thyroid cancer who underwent total thyroidectomy or isthmolobectomy in the PITA TOSCA community, totaling 154 patients consisting of 77 undergoing isthmolobectomy and 77 undergoing total thyroidectomies. Data collection was carried out by interview and questionnaire. The method of selecting subjects was random sampling. The data analysis employed was chi-square to assess the relationship between total thyroidectomy and isthmolobectomy on quality of life. Logistic regression analysis assessed the magnitude of the relationship between variables. The research instrument utilized was the EORTC QLQ C30 questionnaire.Results. The results of the chi-square test exhibited a significant difference in the thyroid cancer group after the sixth month of isthmolobectomy compared to total thyroidectomy with a value of p = <0 xss=removed>Conclusion. Patients with well-differentiated thyroid cancer who underwent isthmolobectomy had better quality of life compared to those who underwent total thyroidectomy after the sixth month compared to the first month after surgery.