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We propose a novel quantum electrodynamics (QED) platform where quantum emitters interact with a Hofstadter-ladder waveguide. We demonstrate several intriguing phenomena stemming from the exotic dispersion relation and vacuum mode properties led by the effective spin-orbit coupling, which have no analog in other QED setups. First, by assuming emitter's frequency to be resonant with the lower band, we find that the spontaneous emission is chiral with most photonic field decaying unidirectionally. Both numerical and analytical results indicate that the Hofstadter-ladder waveguide can be engineered as a well-performed chiral quantum bus. Second, the dynamics of emitters of giant atom form is explored by considering their frequencies below the lower band. Due to quantum interference, we find that both the emitter-waveguide interaction and the amplitudes of bound states are periodically modulated by giant emitter's size. The periodical length depends on the positions of energy minima points induced by the spin-orbit coupling. Last, we consider the interaction between two giant emitters mediated by bound states, and find that their dipole-dipole interaction vanishes (is enhanced) when maximum destructive (constructive) interference happens.