With increased life expectancy among patients with beta-thalassemia major (β-TM) renal insufficiency has been frequently noted because of the persistence of anemia, iron overload and some drug side effects. Serum creatinine becomes elevated in late stage of kidney affection. Cystatin-C is more sensitive biomarker for kidney dysfunction. Our aim was to measure Cystatin-C serum level among patients with β-TM as a marker of early nephropathy. Serum Cystatin-C was measured in 94 patients with β-TM using Enzyme-Linked Immunosorbent Assay (ELISA) and correlated to other clinical, laboratory and radiologic data. Glomerular hyperfiltration was observed in 30.8% while Cystatin-C was elevated in 56.3% of β-TM. Patients having high serum Cystatin-C were older in age and having higher serum levels of aspartate aminotransferases and urea. Cystatin-C level was positively correlated with serum creatinine and urea and negatively correlated with glomerular filtration rate. Periodic assessment of Cystatin-C in patients with β-TM is recommended for early diagnosis of renal dysfunction especially during drug dosing prescription aiming to obtain the maximum effectiveness and safety. Controlling anemia by maintaining appropriate hemoglobin level with close monitoring of iron overload are also recommended to preserve renal function among β-TM patients.