Cosmic rays in galaxies interact with the interstellar medium and give us a direct view of nuclear and particle interactions in the cosmos. For example, cosmic-ray proton interactions with interstellar hydrogen produce gamma rays via pcrpism→ π0→γγ. For a "normal" star-forming galaxy like the Milky Way, most cosmic rays escape the Galaxy before such collisions, but in starburst galaxies with dense gas and huge star formation rate, most cosmic rays do suffer these interactions [1,2]. We construct a "thick-target" model for starburst galaxies, in which cosmic rays are accelerated by supernovae, and escape is neglected. This model gives an upper limit to the gamma-ray emission. Only two free parameters are involved in the model: cosmic-ray proton acceleration energy rate from supernova and the proton injection spectral index. The pionic gamma-radiation is calculated from 10 MeV to 10 TeV for the starburst galaxy NGC 253, and compared to Fermi and HESS data. Our model fits NGC 253 well, suggesting that cosmic rays in this starburst are in the thick target limit, and that this galaxy is a gamma-ray calorimeter.