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Non-invasive early diagnosis of liver cancer is the most effective way to improve the survival rate. In this paper, we developed a label-free and enzyme-free fluorescent biosensor based on target recycling and Thioflavin T (ThT) induced G-quadruplex formation for MXR7 (liver cancer related short gene) detection in human serum. The proposed sensor can detect the target DNA in the concentration range of 0–350 fM with the detection limit as low as 10 fM. Due to the outstanding structural selectivity of ThT for G-quadruplex, this sensor possesses better discrimination ability and higher sensitivity. Furthermore, this enzyme-free and label-free fluorescence sensor has demonstrated to be capable of detecting target DNA in human serum samples because of its high selectivity and sensitivity. The mechanism employed in this study represents a promising path toward directing liver cancer detection in human serum. In addition, this strategy may be extended to detect other cancer related genes by choosing a rational DNA probe according to different sequences of targets. [ABSTRACT FROM AUTHOR]