The stability of alumina-promoted sulfated zirconia (SZA) was investigated to achieve the isomerization of n-butane in a circulating fluidized bed (CFB) unit. The pilot-scale evaluation in a CFB unit showed high stability of the SZA catalyst and that the catalytic activity was dominated by the residence time of n-butane rather than its linear velocity. Increases in the reaction and regeneration temperature both led to an increase in the conversion of n-butane and a decrease in the selectivity to isobutane, caused by increasing side reactions. Although the regeneration was conducted in air, a trace of SO2 evolved during the regeneration, which could be minimized at the appropriate gas stripping temperature, low regeneration temperature, and high space time of the feed. Compared with conventional fixed-bed technologies, the CFB process shows lower selectivity to isobutane due to the inevitable axial back-mixing and severe "dimerization-cracking" reaction.