Recently, DNA tetrahedron-based sensors for intracellular detection have attracted more attention due to many interesting properties, including good structural rigidity, excellent biocompatibility, high resistance to enzymatic degradation, and the ability to enter cells without the use of transfection agents. However, the previous designs are still restricted by their lack of accuracy, reliability, and generality. Herein, to solve these limitations, we describe self-assembly of the competition-mediated FRET-switching DNA tetrahedron molecular beacon (CF-DTMB), and its applications for intracellular tumor-related mRNA detection. In brief, the recognition strand is partially complementary to its competitor, which is a hairpin stem-loop structure inserted in one edge of the DNA tetrahedron. In the absence of a target, a long domain of the recognition strand hybridizes with the competitor and makes the hairpin structure open, inducing the two labeled dyes to be spatially separated (FRET off). However, in the ...