The highly sensitive detection and imaging of enzymatic activities in vivo could provide effective information about biological functions for monitoring the process of disease and evaluating the effect of therapy. 19F magnetic resonance imaging (MRI) has attracted wide interest because of its deep tissue imaging capability and negligible endogenous background interference, which are suitable for the visualization of enzymatic activities in vivo, but the fabrication of this probe faces challenges. Here, we report nanoprobes with turn-on 19F MRI for sensing the activity of phospholipase A2 (PLA2). These nanoprobes are composed of Gd3+-exchanged NaYF4:Yb3+/Er3+ upconversion luminescent nanoparticles grafted with perfluoro-15-crown-5-ether (PFCE) as the hydrophobic core with a phospholipid shell in which the 19F MRI signal of PFCE is obviously quenched by adjacent Gd3+. The shielded 19F MRI signal of these nanoprobes is then turned on by the nanoprobe dissolution stemming from phospholipid hydrolysis by PLA2 and increases linearly along with the increment of PLA2 in the range of 5.0-200 U/L. Apart from the in vitro detection of PLA2 by 19F NMR, these nanoprobes show great potential for both the in vivo 19F MRI sensing of PLA2 and activity screening of PLA2 inhibitors with a high signal-to-noise ratio and a high penetration depth.