Lanthanide-doped metal-organic frameworks (Y/Yb/Er-MOF) were synthesized by a low-cost solvothermal method. The obtained Y/Yb/Er-MOF shows the cooperative upconversion luminescence of Yb3+ and upconversion luminescence of Er3+ (Yb3+-sensitized) irradiated by a continuous wave 980 nm laser. In order to explore the potential application of Y/Yb/Er-MOF in relative humidity (RH) sensors, the RH responsiveness of Y/Yb/Er-MOF was investigated by measuring the intensity changes of upconversion luminescence. The Y/Yb/Er-MOF possesses two luminescence centers, in which Yb3+ forms emission at 500 nm through the cooperative luminescence effect, and Er3+ achieves 660 nm emission through excited state absorption and successive energy transfer from Yb3+. Hence, the ratio meter luminescence sensor for RH is constructed based on Y/Yb/Er-MOF. The results show that the response of Y/Yb/Er-MOF to RH presents a linear relationship in the range of 11–95%. The cycle stability of Y/Yb/Er-MOF responses to RH was investigated with the intensity changes of upconversion luminescence, and the recovery ratio was more than 93% each time. Therefore, the Y/Yb/Er-MOF is a humidity-sensitive material with great potential for applications such as humidity sensors.