We study in detail the pattern of anomaly cancellation in D = 6 Type IIB ZN orientifolds, occurring through a generalized Green-Schwarz mechanism involving several RR antisymmetric tensors and scalars fields. The starting point is a direct string theory computation of the inflow of anomaly arising from magnetic interaction of D-branes, O-planes and fixed-points, which are encoded in topological one-loop partition functions in the RR odd spin-structure. All the RR anomalous couplings of these objects are then obtained by factorization. They are responsible for a spontaneous breaking of U(1) factors through a Higgs mechanism involving the corresponding hypermultiplets. Some of them are also related by supersymmetry to gauge couplings involvin...