Upconversion nanoparticles (UCNPs) are promising energy donors for luminescence resonance energy transfer (LRET) and have widely been used to construct nanoprobes. To improve the LRET efficiency, which is currently a limiting factor for UCNPs-based bioassay, we herein propose a strategy to construct LRET-based nanoprobe using UCNPs with confined emitters and bared surface as the luminophore, with Ca(2+) as the proof-of-concept target. The sandwich-structure upconversion nanoparticles (SWUCNPs) are designed with a core-inner shell-outer shell architecture, in which the emitting ions (Ln(3+)) are precisely located in the inner shell near the particle surface, which is close enough to external energy acceptors. The target receptor (Fluo-4) is directly tagged on bared surface of SWUCNPs, which further reduces the donor-to-acceptor distance. Our strategy contributes to significantly improved LRET efficiency and hence affords an ultrahigh sensitivity for Ca(2+) detection. The as-constructed nanoprobe is structurally stable and exhibits good biocompatibility, which ensures uptake and reliable observation in living cells. The nanoprobe can be used for monitoring the different levels of cytosol [Ca(2+)] in living cells. Furthermore, it is applicable in Ca(2+) imaging in mice liver tissues.