This paper reports the application of the biomolecular probe sensor based on the tilted fiber Bragg grating (TFBG) surface plasma resonance (SPR) which can recognize the specificity of the specific molecule by depositing sensitive biological membrane outside the active golden layer. The method of self-assembly was used to make the fixed sensitive biological membrane to achieve the best effect in the experiment. To illustrate the specific recognition of the DNA molecule, the TFBG-SPR biosensor was exposed to complementary DNA solutions with the concentration of 0.1 mmol/L and 0.05 mmol/L, respectively. The resonance wavelength of the TFBG-SPR biosensor increased gradually, indicating that the hybridization with the complementary DNA molecules changed the effective refractive index in the vicinity of the golden layer. Furthermore, the results illustrated the feasibility of the biomolecular probe sensor based on the TFBG surface plasma resonance for detecting the specific molecule.