This paper develops a facile solution-based method to synthesize hollow Cu2-xTe nanocrystals (NCs) with tunable interior volume based on the Kirkendall effect. Transmission electron microscopy images and time-dependent absorption spectra reveal the temporal growth process from solid copper nanoparticles to hollow Cu2-xTe NCs. Furthermore, the as-prepared hollow Cu2-xTe NCs show enhanced sensitivity for the detection of carbon monoxide (CO), which is often referred to as the “silent killer”. The response and recovery time of the as-prepared sensor for the detection of 100 ppm CO gas are estimated to be about 21 and 100 s, respectively, which are sufficient to render it a promising candidate for effective CO gas-sensing applications. Such enhanced performance is achieved owing to the small grain size and large specific area of the hollow nanostructures. Therefore, the obtained hollow NCs based on the Kirkendall effect may have the potential as new functional blocks for high-performance gas sensors.