The upconversion lasing through simultaneous multiphoton absorption (MPA) is a high-order nonlinear optical process, which enables many critical applications in the fluorescence imaging probe, laser tomography, and photodynamic therapy. Herein, the upconversion lasing from microwires via simultaneous six-photon absorption at room temperature is first realized. Moreover, the lasing peak and third-harmonic generation peak of pumping light are observed concurrently, while the temperature-dependent spectrum elucidates the essential distinction between each other. In addition, the low-threshold six-photon excited whispering-gallery mode lasing based on strong optical confinement of the hexagonal microcavity is investigated comprehensively. The results prove that it is feasible to realize high-order MPA upconversion lasing using high Q-factor microcavity, which can be promoted to other wide bandgap semiconductor micro-/nanostructure to generate frequency upconversion lasing.