The selective detection of dangerous and explosive gases with high sensitivity is serious problem to safety of humans and industrial processes. Small sized nanoparticles aggregated into a nanospheres offer plenty of advantages such as large specific area, greater mass transportation, and diffusion of gas molecules deep inside the material towards efficient gas sensing applications. Herein, In2O3 nanoparticles aggregated into nanospheres were synthesized successfully through one step microwave hydrothermal method. The structure, morphology and chemical states of prepared In2O3 nanospheres were studied by XRD, TEM and XPS measurements. Furthermore, obtained In2O3 nanospheres were applied as a gas sensing layer for acetaldehyde (CH3CHO) detection. Acetaldehyde is an important volatile organic compound which is highly reactive, toxic and carcinogenic agent. Gas sensor based on In2O3 nanospheres shows high sensitivity for a wide range of CH3CHO concentration (1–100 ppm). Concentration dependent resistances during the exposure and oxidation reaction of CH3CHO gas were investigated. The obtained results in this work indicate that In2O3 nanospheres are prospective candidates for the fabrication of CH3CHO gas sensors.