In order to acquire a miniature refractive index (RI) biosensor with high sensitivity, fast and selective for ultra-low concentrations of molecules, a new Photonic Crystal (PhC) biosensor based on a waveguide coupled to a Fano resonator is proposed for cancer cells detection. An optimized structure of the biosensor can detect cells cancers (Besal, Hela, Jurkat and PC12) in a biological solution deposited on the surface of the resonator. The detection mechanism uses the refractive index as a detection element. The performance of the proposed biosensor is studied by analyzing the variations in the transmission spectrum of different normal and cancer cells. The proposed structure is multimode PhC, with silica as a dielectric material. The finite element method (FEM) have been implemented for studying and investigating the numerical values. The simulation results display that the proposed biosensor attains spectral sensitivities of ‘513.12 nm RIU−1’, ‘587.28 nm RIU−1 ’, ‘702.35 nm RIU−1 ’ and ‘690.57 nm RIU−1 ’ corresponding to Hela cells, PC12 cells, Basal cells and Jurkat cells, respectively. And he qualilty factor Q of the Fano resonance mode can reach 3040.26. Our optimized design ensures easy fabrication with ongoing techniques. This study may open a new way for the development of integrated optical circuits and biosensing.