Background: Although differentiated thyroid cancer (DTC) has a low disease-specific mortality, this does not reflect their patients' personal experience of the disease. Health related quality of life (QOL) of thyroid cancer survivors have not been well studied in Arab countries especially in Egypt. Objective: This study aimed to assess QOL of DTC patients during and after withdrawal of treatment with L thyroxin. Method: a case control study was conducted in Sohag Institute of Cancer, Egypt, using the 36- SF QOL questionnaire among 89 DTC patients and 100 cancer free persons matched by age, sex, educational and socioeconomic level. QOL of DTC patients were assessed twice during treatment with Eltroxin (base line QOL) and after three weeks of its withdrawal. Results: the mean age (SD) of the studied participants was 39 (1.4) years. The majority were female, rural residents and illiterate (70.7%, 88.7% and 85.3% respectively). They reported lower base line QOL in six of the eight domains of 36- SF questionnaires. Physical Component summary (PCS) and Component Summary (MCS) mean score were 75.7 (22.0) and 67.3 (23.2). Significantly reduced QOL of the studied participants was reported after LT4 withdrawal. Both PCS and MCS were significantly higher among patients whose age was lower than 45 years, and those who were followed up for more than three years. Conclusion: DTC survivors in Sohag, Egypt, showed decreased quality of life which became worse during every surveillance cycle as a result of stopping LT4 treatment and older DTC survivors suffers a lot and need better treatment and surveillance regimen.