In this work, highly sensitive D-shaped photonic crystal fiber (PCF) sensor with plasmonic pyramid grating is introduced and analyzed. The sensing mechanism depends on the coupling between the fundamental core mode and the surface plasmon mode around the plasmonic pyramid grating. The resonance frequency depends on the analyte refractive index (RI) which can be employed to detect the analyte RI changes. The geometrical parameters of the proposed PCF and gold pyramid grating are studied to enhance the RI sensor sensitivity. The simulation results are obtained using full vectorial finite element method. The suggested sensor has higher sensitivity of 5200 nm/RIU than 3340 nm/RIU of the conventional grating design through the studied RI range from 1.355 to 1.385. Therefore, the reported RI sensor can be used for basal cancer cell detection with normal and cancerous cells’ refractive indices of 1.36 and 1.38, respectively. Additionally, linear performance is achieved using the reported design.