Nanosized Yb3+ and Er3+ co-doped beta-NaYF4 cores coated with multiple beta-NaYF4 shell layers were synthesized by a solvothermal process. X-ray diffraction and scanning electron microscopy were used to characterize the crystal structure and morphology of the materials. The visible and near-infrared spectra as well as the decay curves were also measured. A 40-fold intensity increase for the green upconversion and a 34-fold intensity increase for the red upconversion were observed as the cores are coated with three shell layers. The origin of the upconversion enhancement was studied on the basis of photoluminescence spectra and decay times. Our results indicate that the upconversion enhancement in the sandwiched structure mainly originates from the suppression of de-excitation of Yb3+ ions. We also explored the population of the Er(3+)4F(9/2) level. The results reveal that energy transfer from the lower intermediate Er(3+)4I(13/2) level is dominant for populating the Er(3+)4F(9/2) level when the nanocrystal size is relatively small; however, with increasing nanocrystal size, the contribution of the green emitting Er(3+)4S(3/2) level for populating the Er(3+)4F(9/2) level, which mainly comes from the cross relaxation energy transfer from Er3+ ions to Yb3+ ions followed by energy back transfer within the same Er3+-Yb3+ pair, becomes more and more important. Moreover, this mechanism takes place only in the nearest Er3+-Yb3+ pairs. This population route is in good agreement with that in nanomaterials and bulk materials.