A novel electrochemical cocaine aptamer biosensor based on quantum dots (QDs) as immobilized substrate, utilizing the advantage of sulfur-sulfur affinity, together with the high combination ability between heavy metal ion of quantum dots and sulfhydryl group of aptamer, has been proposed. Some intact aptamer have especial structure, such as hairpin structure and intrinsic binding site, which make the proposed electrochemical aptamer biosensor more sensitive and feasible after structure switching induced by targets. [Ru(NH3)(6)](3+) and [Fe(CN)(6)](3-/4-) have been used as electroactive redox probe. Due to the distinct electrostatic interaction between electroactive probes and the negatively charged phosphate backbone of aptamers, different response types (signal-on and signal-off) have been obtained respectively. The linear range covered from 1 x 10(-9) mol L-1 to 1 x 10(-6) mol L-1 with correlation coefficient of 0.9765 while using [Ru(NH3)(6)](3+) as probe and 1 x 10(-7)-1 x 10(-6) mol L-1 with correlation coefficient of 0.9839 while using [Fe(CN)(6)](3-/4-) as probe. It turns out to be that the response of proposed electrochemical aptasensor using cationic probe is much better than that of using anionic probe. The biosensor has high selectivity, good specificity, stability, reusability and practicability and can be extended to the determination of other small molecules. (C) 2011 Elsevier B.V. All rights reserved.