Neuroinflammation induced by microglial activation has recently attracted attention as a cause of neurodegenerative diseases, such as Alzheimer’s disease (AD). Candida albicans is a prevalent fungal species in human microbiota, and suspected of causing AD through neuroinflammation, as C. albicans has been detected in the brain tissue of AD patients, and the intravenous injection of C. albicans induced mild memory impairment, accompanied by C. albicans invasion of the brain and neuroinflammation in mice. However, the detailed mechanism by which C. albicans induces neuroinflammation remains unclear. In this study, we showed that candidalysin, a cytolytic peptide toxin secreted by C. albicans, induces the production of the inflammatory cytokine IL-6 accompanied by nuclear translocation of nuclear factor-kappaB (NF-κB) through the degradation of inhibitor of κBα (IκBα) in the human microglial cell line HMC3. We also found that candidalysin induced autophagy, and that an autophagy inhibitor suppressed candidalysin-induced IκBα degradation, nuclear translocation of NF-κB, and IL-6 mRNA expression. These findings suggest that candidalysin triggers autophagy, which induces inflammatory responses via NF-κB in human microglia. Thus, the present study may have uncovered an important pathway for neuroinflammation via microglia when C. albicans invades the brain.