The Sb2O4∶Yb3+, Tm3+ up-conversion luminescence powder with excellent physical, chemical stability and relative low phonon energy was synthesized by the high temperature solid-state reaction and its up-conversion luminescence property was investigated. Under the 980 nm excitation, infrared and blue up-conversion emissions centered at 800 and 480 nm were observed, which were assigned to the 1G4→3H6 and 3H4→3H6 transitions of Tm3+, respectively. The influence of Yb3+ and Tm3+ concentration on the up-conversion emission property was also obtained. The up-conversion luminescence increases with increasing of Yb3+ and Tm3+ concentration. Additionally, the up-conversion luminescence mechanism was discussed based on the dependence of Tm3+ up-conversion luminescence on pump power. It is interesting that two photon excitation processes for blue and infrared emission were observed in the Sb2O4∶Yb3+, Tm3+ powder under a 980 nm excitation. Based on the energy level diagram of Tm3+ and Yb3+ ions, we think that two photons blue emission is contributed to the cooperation energy transfer between Tm3+ and Yb3+ ions. We believe that the Sb2O4∶Yb3+, Tm3+ up-conversion luminescence powder will have potential application for new optical devices in up-conversion color displays, sensors, detection of infrared radiation, and lasers.