In situ high-pressure Raman spectra of S-trioxane have been measured up to 28 GPa. A first-order phase transition was detected at ~3 GPa from the splitting, newly existing and diminishing of the internal modes and from changes in the slope on plots of frequency versus pressure. The vibrational spectra and theoretical simulation indicate that the isolated molecule structure changes from puckered to very puckered structure at the first phase, while at the beginning of the second phase, S-trioxane goes back to its original puckered structure and loses its C3 axis; then, it changes to planar structure at about ~GPa and keeps its flat structure in the second phase up to the highest pressure studied. We believe that phase may be a dominant factor responsible for the pressure-induced planar molecular geometry, providing a reasonable explanation for the experimental observations.