Because circulating tumor cells (CTCs) have been proven to be an important clue of the tumor metastasis, their detection thus plays a pivotal role in the diagnosis and prognosis of cancer. Herein, we fabricate an electrochemical sensor by directly conjugating two cell-specific aptamers, TLS1c and TLS11a, which specifically recognize MEAR cancer cells, to the surface of a glassy carbon electrode (GCE) via the formation of amide bonds. The two aptamers are simultaneously conjugated to the GCE surface via precisely controlled linkers: TLS1c through a flexible linker (a single-stranded DNA T15; ss-TLS1c) and TLS11a through a rigid linker (a double-stranded DNA T15/A15; ds-TLS11a). It is found that such ss-TLS1c/ds-TLS11a dual-modified GCEs show greatly improved sensitivity in comparison with those modified with a single type of aptamer alone or ds-TLS1c/ds-TLS11a with both rigid linkers, suggesting that our optimized, rationally designed electrode-aptamer biosensing interface may enable better recognition and thus more sensitive detection of tumor cells. Through the utilization of this dual-aptamer-modified GCE, as few as a single MEAR cell in 10(9) whole blood cells can be successfully detected with a linear range of 1-14 MEAR cells. Our work demonstrates a rather simple yet well-designed and ultrasensitive tumor cell detection method based on the cell-specific aptamer-modified GCE, showing a promising potential for further CTC-related clinical applications.