This work presents a paper spray mass spectrometry-based method, to analyze microdroplets produced in a gravity-driven microchip. Droplets at ambient pressure were passively transferred from the chip to a paper substrate by the capillary wicking effect. Paper spray ionization was then performed for mass spectrometry (MS) analysis of droplet contents. The qualitative and quantitative analytical performances of this technique for single droplets were demonstrated. This manually controlled interface is straightforward, low-cost and simple to implement. Moreover, paper spray ionization MS holds promise in the direct analysis of real biological/chemical microreaction samples because of its tolerance with complex matrices. As a proof-of-concept example, the droplet-based acetylcholine hydrolysis was carried out to demonstrate the validation of our method for the direct analysis of micro-chemical/biological reactions. We also introduced a flow injection analysis (FIA) system combined with our droplet system to generate a concentration gradient. As a result, the microreaction can be performed at different concentrations and kinetic information can be obtained in one sample injection. In conclusion, the combination of a microdroplet chip with paper spray ionization and the introduction of the FIA system and make our droplet-MS scheme a useful platform for monitoring and analyzing organic-phase chemical/biological reactions.