In most animals, avoiding pathogenic bacteria is crucial for better health and a long life span. For this purpose, animals should be able to quickly sense the presence or uptake of pathogens. The intestine could be a candidate organ to induce escape behaviors; however, the intestinal signaling mechanism for acute regulation of neuronal activity is not well understood. Here, we show that adult Caenorhabditis elegans can respond to the pathogenic bacterium Pseudomonas aeruginosa within 30 min of exposure. This behavior was much faster than previously observed avoidance behaviors in response to P. aeruginosa. By genetic screening, we isolated a mutant defective in this quick avoidance behavior and found that the novel F-box protein FBXC-58 is involved. FBXC-58 is expressed in several tissues, but defective avoidance was rescued by expression of the protein in the intestine. Interestingly, we also found that some but not all mutants in the p38-MAPK and insulin-like signaling pathways, which function in the immune response to pathogens in the intestine, were defective in the quick avoidance behavior to P. aeruginosa. These results suggest that a novel signaling pathway in the intestine exists to regulate neuronal activity for a quick behavioral response.