A new hollow-core metal-cladding waveguide (HCMW) has been proposed in order to design and realize optical biosensor for the direct liquid probing. Two peculiar properties are exhibited with respect to the current evanescent wave sensors. First, the effective index of the HCMW can exist in the region of 0<N<1, which is usually prohibited for the conventional guided modes and the surface plasmon resonance modes. Second, the analyte to be detected does not locate in the evanescent field but in the oscillating field. Glucose solution is utilized to characterize the device performance. According to the reflectivity changes and the signal-to-noise ratio, the new biosensor has been shown to be capable of directly detecting concentration of glucose as low as 0.5ppm, which corresponds to a high resolution of 1.4×10−7 RI units. This new biosensor improves the detection limitation and shortens the analysis time significantly.