© 2018, Springer Science+Business Media, LLC, part of Springer Nature. We used in situ measurements of X-ray diffraction patterns in a cubic multi-anvil press at pressures up to 3 GPa and at 500–1300 K to examine thermal expansion and its pressure dependence in (Mg0.73Fe0.27)(Cr0.56Al1.44)O4 spinel separated from a mantle-derived xenolith. Thermal expansion of mantle minerals is considerably important to examine thermodynamic properties of mantle. Nevertheless, no report of the relevant literature describes a study investigating the thermal expansion of natural mantle spinel under the P–T conditions presented above. Cell volume of the natural spinel increased concomitantly with increasing temperature, enabling us to estimate thermal expansion coefficients. The relation between the cell volume and pressure at 700 K is distinct in slope from those of adjacent temperature, perhaps because of the transition of spinel from order to disorder. Pressure dependence of thermal expansion coefficients was not identified. Reports of some earlier studies have described various values of thermal expansion coefficients of MgAl2O4: αmean = 1.70–2.94 × 10−5 K−1. The obtained mean thermal expansion coefficient (2.66 × 10−5) is slightly higher than the reported values. This slight difference might be inferred as reflecting the effects of the presence of Fe and Cr, respectively, at sites A and B.