A series of MgF2-modified hydrotalcite-like (HT) derivatives supported Pt-In catalysts PtInHTR-X (X = NH4F, NaF and KF, R = reduced catalyst) were prepared by combination of hydrothermal method, alkali-etching and impregnation strategy and applied to direct dehydrogenation of isobutane to isobutene. The catalysts and precursors were characterized by XRD, SEM, TEM, XPS, TG, O2-TPO and low temperature N2 adsorption-desorption isotherms. The formation of MgF2 phase as dopant to modify the catalyst can influence the pore structure and even the surface acid properties of catalysts. Especially, compared with the three catalysts, PtInHTR-KF catalyst had better stability of isobutene selectivity of over 95% after 9 h reaction, and PtInHTR-NH4F and PtInHTR-NaF catalysts exhibited more stable isobutane activity of 60%. One of the reasons for this catalytic performance is that small particles of MgF2 and unsaturated MgF2 can provide weak acidic sites which can inhibit coke deposition. And it was found the improved catalytic performance was also related to the appropriate In3+/In0 ratio, well-dispersed Pt species and the excellent anti-sintering ability of catalysts modified MgF2.