The interaction of the Puppis A supernova remnant (SNR) with a neighboring molecular cloud provides a unique opportunity to measure the amount of grain destruction in an SNR shock. Spitzer Space Telescope MIPS imaging of the entire SNR at 24, 70, and 160 μm shows an extremely good correlation with X-ray emission, indicating that the SNR's IR radiation is dominated by the thermal emission of swept-up interstellar dust, collisionally heated by the hot shocked gas. Spitzer IRS spectral observations targeted both the Bright Eastern Knot (BEK) of the SNR where a small cloud has been engulfed by the supernova blast wave and outlying portions of the associated molecular cloud that are yet to be hit by the shock front. Modeling the spectra from both regions reveals the composition and the grain size distribution of the interstellar dust, both in front of and behind the SNR shock front. The comparison shows that the ubiquitous polycyclic aromatic hydrocarbons of the interstellar medium are destroyed within the BEK, along with nearly 25% of the mass of graphite and silicate dust grains.