In this work, we demonstrate improved molecular detection sensitivity for silicon slab photonic crystal cavities by introducing multiple-hole defects (MHDs), which increase the surface area available for label-free detection without degrading the quality factor. Compared to photonic crystals with L3 defects, adding MHDs into photonic crystal cavities enabled a 44% increase in detection sensitivity towards small refractive index perturbations due to surface monolayer attachment of a small aminosilane molecule. Also, photonic crystals with MHDs exhibited 18% higher detection sensitivity for bulk refractive index changes.