Abstract We study proton decay in a six-dimensional orbifold GUT model with gauge group SO(10)×U(1) A . Magnetic U(1) A flux in the compact dimensions determines the multiplicity of quark-lepton generations, and it also breaks supersymmetry by giving universal GUT scale masses to scalar quarks and leptons. The model can successfully account for quark and lepton masses and mixings. Our analysis of proton decay leads to the conclusion that the proton lifetime must be close to the current experimental lower bound. Moreover, we find that the branching ratios for the decay channels p → e + π 0 and p → μ + π 0 are of similar size, in fact the latter one can even be dominant. This is due to flavour non-diagonal couplings of heavy vector bosons together with large off-diagonal Higgs couplings, which appears to be a generic feature of flux compactifications.