Zirconia-based catalysts were synthesized by various methods and were evaluated for the synthesis of isobutane and isobutene from CO hydrogenation. The methods of preparation included precipitation (ZrO2 (PPT)), calcination of zirconyl salt (ZrO2 (H-0304)), and a modified sol-gel method (ZrO2 (sol-gel)). Acid-base properties of zirconia were affected by the method of preparation. The number of acidic sites on the surface follows the order of ZrO2 (PPT) > ZrO2 (sol-gel) approximate to ZrO2 (H-0304), and the number of basic sites follows ZrO2 (PPT) > ZrO2 (sol-gel) > ZrO2 (H-0304). Furthermore, adding aluminum increased the numbers of acidic and basic sites, and adding silicon increased the number of acidic sites but reduced the number of basic sites. The product distribution of CO hydrogenation depended on the acid-base properties of the catalyst, and the activity tests indicated that a large ratio of basic to acidic sites is a requirement for an active catalyst to produce isobutane and isobutene from CO hydrogenation.