Neutrino interactions with stellar material are widely believed to be fundamental to the explosion of massive stars. However, this important process has remained difficult to confirm observationally. We propose a new method to verify it using X-ray observations of the supernova remnant Cassiopeia A. The elemental composition in its Fe-rich ejecta that could have been produced at the innermost region of the supernova, where neutrinos are expected to interact, allows us to examine the presence of neutrino interactions. Here we demonstrate that the amount of Mn produced without neutrino nucleosynthesis processes (i.e., the ν- and νp-processes) is too small to explain the Mn/Fe mass ratio we measure (0.14%–0.67%). This result supports the operation of significant neutrino interactions in the Cassiopeia A supernova. If the observed Mn/Fe mass ratio purely reflects the production at the innermost region of the supernova, this would be the first robust confirmation of neutrino–matter interactions in an individual supernova. We further show that the Mn/Fe mass ratio has the potential to constrain supernova neutrino parameters (i.e., total neutrino luminosity, neutrino temperature). Future spatially resolved, high-resolution X-ray spectroscopy will allow us to investigate the details of neutrino–supernova astrophysics through its signatures in elemental composition not only in Cassiopeia A but also in other remnants.