Abstract The Japanese Hayabusa spacecraft successfully carried out in situ observations of S-class asteroid 25143 Itokawa, including the surface major elemental analysis with the X-ray fluorescence spectrometer (XRSHayabusa). Our previous results for the X-ray experiments (Okada et al., 2006a) indicated that major elemental ratios of Mg/Si and Al/Si on the surface of Itokawa resemble ordinary LL- or L-chondrites more than any other meteorite analogues. In the NEAR Shoemaker observations of S-class asteroid 433 Eros, the results of X-ray fluorescence observations indicated the depletion of sulfur, probably reflecting impact-induced volatilization, photoor ion-induced sputtering at the surface, or the loss of FeS-rich materials due to partial melting. Here, we determined the elemental abundance of sulfur (S) on the surface of Itokawa, in addition to that of Mg, Al, and Si, and its regional variation using XRS-Hayabusa observations. In particular, we carefully corrected the fluctuation of solar X-rays, variation of surface geometry, and sensor response function in this analysis, and thus we believe that the results are more accurate than those of our previous report. In this study, the upper and lower limits for Mg/Si, Al/Si, and S/Si overlap those of meteorite analogues for ordinary chondrites or primitive achondrites. In terms of the major elemental composition, Itokawa is best classified as a ordinary chondrite or a primitive achondrite. Our models do not include the mineral mixing effects. With the effects, the abundance of sulfur is expected to be 30% lower than our results. Hence, we conclude that the abundance of sulfur on the surface of Itokawa is almost equal to or even lower than the average abundance in ordinary chondrites. Although the abundances for Mg and Si are globally homogeneous, best-fit or upper limits of mass fraction for Al and S vary in local areas. There is a negative correlation (−0.92) for Al/Si vs. S/Si in ten facets. In particular, the area with the lowest sulfur, accompanied with enriched aluminum, is found in Arcoona, close to a cratered area. Therefore, aluminum enrichment and sulfur depletion features may support events of partial melting on the parent body of Itokawa or aluminum-rich material impacts on the surface of Itokawa. In some areas, Itokawa has a brighter geometric albedo and color variation. Little altered, fresh material may be exposed in these portions of the surface. The sulfur abundance on the surface appears to vary between little and highly altered areas by space weathering. Thus, the sulfur regional variation in our result may reflect the heterogeneity of a surface altered by space weathering.