PURPOSE: To explore the acute effect of betel quid (BQ) use on functional network connectivity by comparing the global functional brain networks and their subsets before and immediately after BQ chewing. MATERIALS AND METHODS: Resting-state functional magnetic resonance imaging (fMRI) was performed in 27 healthy male participants before and just after chewing BQ on a 3.0T scanner with a gradient-echo echo planar imaging sequence. Independent component analysis (ICA) was used to determine components that represent the brain's functional networks and their spatial aspects of functional connectivity. A paired t-test was used for exploring the connectivity differences in each network before and after BQ chewing. RESULTS: Sixteen networks were identified by ICA. Nine of them showed connectivity differences before and after BQ chewing (P < 0.05 false discovery rate corrected): (A) orbitofrontal, (B) left frontoparietal, (C) visual, (D) right frontoparietal, (E) anterior default mode, (F) medial frontal/anterior cingulate (G) frontotemporal, (H) occipital/parietal, (I) occipital/temporal/cerebellum. Moreover, networks A, B, C, D, G, H, and I showed increased connectivity, while networks E and F showed decreased connectivity in participants after BQ chewing compared to before chewing. CONCLUSION: The acute effects of BQ use appear to actively alter functional connectivity of frontal and default networks that are known to play a key role in addictive behavior. LEVEL OF EVIDENCE: 2 J. Magn. Reson. Imaging 2017;45:157-166.