Abstract Tumor necrosis factor (TNF)-α promotes rheumatoid arthritis (RA) symptoms, including inflammation and bone erosion. The role of TNF-α in RA is considered to be complex because cytokine is responsible for a wide-range of functions, such as activation of immune cells, stimulation of osteoclast differentiation, and induction of cellular apoptosis. It has appeared that the determination of TNF-α concentration in serum might be helpful in the staging and prognosis of diseases. In this study, a simple and sensitive potentiometric sensor method has described for the determination of TNF-α in serum. Influences of the membrane composition, concentration and equilibrium time have been investigated on the response properties of the electrode. The sensor has exhibited a visibly enhanced response toward TNF-α over the concentration range of 0.1–1.0 mg L −1 with a lower detection limit (LDL) of 0.015 mg L −1 and a slope of 62.2 mV decade −1 . The sensor has demonstrated a quick and reliable response, ability to be reproduced, as well as long-term stability.