Detecting xylene gas is an important means of avoiding human harm from gas poisoning. A precise measurement demands that the gas sensor used must have high sensitivity, high selectivity, and low working temperature. To meet these requirements, in this study, Sn2+-doped NiO flower-like microspheres (SNM) with different amounts of Sn2+ synthesized by a one-step hydrothermal process were investigated. The responses of gas sensors based on different Sn2+-doped NiO materials for various targeting gases were fully characterized. It was found that all of the synthesized materials exhibited the best gas response at a working temperature of 180 degrees, which was much lower than the previously reported working temperature range of 300–500 degrees. When exposed to 10 ppm xylene, the 8 at% Sn2+-doped NiO sensor (mol ratio) exhibited the highest response, with a value of 30 (Rg/Ra). More significantly, the detection limit of the 8 at% Sn2+-doped NiO sensor for xylene is down in the ppb level. The Sn2+-doped NiO material also exhibits excellent selectivity for other gases with long-term stability and repeatability. The significant improvement in the response to xylene can theoretically be attributed to a decrease in the intrinsic hole carrier concentration, higher amounts of adsorbed oxygen and active sites.