Although the moisture feedback has been well known to be essential in the Madden-Julian Oscillation (MJO) dynamics, whether its pre-moistening effect plays a key role in exciting the onset of primary MJO events, as has been confirmed in the successive initiation, remains elusive. In this study, using a hybrid coupled climate model that has a good fidelity in simulating the intraseasonal variability, we develop a new framework of methodology to investigate the nonlinear excitation of primary MJO event, of which the key achievement is the successful implementation of the conditional nonlinear optimal perturbation (CNOP). In an application of this new framework, the CNOP-type moisture perturbations are calculated for the pre-chosen non-MJO reference states and generally favor a moistening in the equatorial region while drying in the poleward. Comparisons of the model simulation with observation give credibility to the existence of moisture signals several weeks before some primary MJO events. A suite of numerical experiments confirms that the CNOPs of moisture can contribute to the excitation and propagation of strong primary MJO events while random perturbations cannot. The moisture budget analysis further reveals the central importance of the horizontal moisture advection, especially the nonlinearly upscaled moisture transports associated with the high-frequency disturbances on the quasi-3-4-day and 6-8-day synoptic time scales, in supporting the nonlinear excitation of the primary MJO events. The subgrid-scale processes of evaporation, condensation and eddy transport of moisture are found to be critical for the pre-moistening effect in the boundary layer as well. This study directly supports the vital importance of the moisture perturbations, which are characterized by a particular pattern concentrated at low levels, to the nonlinear growth and propagation of the primary MJO events.Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.