Aimed at a high-performance biosensor for sensing biological molecules quickly and accurately, a novel nonuniform photonic crystal waveguide (NUPhCW) with a feedback loop is systematically investigated based on the mode-splitting effect. Thanks to the careful design of the nonuniform holes of NUPhCW with a feedback loop, the Autler-Townes splitting occurs in our device, and the spacing of two splitting resonance modes changes with the environmental refractive index, which is beneficial for achieving biosensing scenarios. Further, this integrated structure allows for self-referencing detection for immunity against environmental noise. Sensitivity of the NUPhCW is achieved at ∼117 nm/RIU, which is 2.6 times more than that of the common microring resonator, indicating that our proposed device structure would be promising for high-quality optical label-free sensing.