Plant fatty acids and lipids have essential functions in storing energy and acting as structural components for cell membranes. They are critical for plant growth and defense. Acyl Carrier Protein (ACP) is a small acidic protein, which can carry the acyl group to elongate fatty acid chains. The Arabidopsis thaliana ACP family has 8 ACP members. By applying integrated genetic, molecular, and biochemical approaches, we have discovered that one member of ACPs functions as a broad negative regulator in plant immunity, since the mutant plants can enhance plant resistance against the bacterial pathogen Pseudomonas syringae and fungal pathogen Botrytis cinerea. The comparative analysis of fatty acid levels and related gene expression in diverse defense-related pathways indicated that the acp mutant may enhance plant disease resistance through up-regulating the Salicylic Acid (SA) pathway and repressing the Jasmonic Acid (JA) pathway. The increased callose deposition of mutant may also contribute to the enhanced disease resistance. Hormone contents and reactive oxygen species levels of the mutant plants will be further investigated. It is found that this ACP interacts with an uncharacterized TIR-NBS (TN) protein that functions in plant defense based on our result. However, the functional mechanism of their interaction in plant disease resistance are not known. Our further investigation of the related mechanisms and networks will strengthen our understanding of the function of the ACP and TN proteins in plant immunity and their applications for enhancing plant health and yield.