Drawing on social exchange theory, this study explores the relationship between high-performance work systems (HPWS) and proactive work behavior. We also examined whether perceived organizational support (POS) mediated the effects of HPWS on supervisor ratings of followers’ proactive behavior. The results from structural equation modeling and hierarchical regression analyses showed that HPWS were positively related to proactive behavior. The results also suggest that POS mediated the relationship between HPWS and proactive behavior. The theoretical and practical implications of these findings are discussed