We set the strongest limits to date on the velocity-independent dark matter (DM)-proton cross section σ for DM masses m=10 keV to 100 GeV, using large-scale structure traced by the Lyman-alpha forest: e.g., a 95% lower limit σ<6×10^{-30} cm^{2}, for m=100 keV. Our results complement direct detection, which has limited sensitivity to sub-GeV DM. We use an emulator of cosmological simulations, combined with data from the smallest cosmological scales used to date, to model and search for the imprint of primordial DM-proton collisions. Cosmological bounds are improved by up to a factor of 25.