This paper reports an optical "TURN OFF" aptasensor, which is comprised of a deoxyribonucleic acid aptamer attached to a quantum dot on the terminus and gold nanoparticle on the terminus. The photoluminescence intensity is observed to decrease upon progressive addition of the target protein tumor necrosis factor-alpha (TNF- ) to the sensor. For PBS-based TNF- samples, the beacon exhibited 19%-20% quenching at around 22 nM concentration. The photoluminescence intensity and the quenching efficiency showed a linear decrease and a linear increase, respectively, between 0 to 22.3 nM TNF- . The detection limit of the sensor was found to be 97.2 pM. Specificity test results determined that the sensor has higher selectivity toward TNF- than other control proteins such as C-reactive protein, albumin, and transferrin. The beacon successfully detected different concentrations of TNF- in human serum-based samples exhibiting around 10% quenching efficiency at 12.5 nM of the protein.