Hsp70 proteins are a well‐known class of chaperones that have also been described to have roles in cellular regulation. Here, we show that a Cryptococcus neoformans Hsp70 homologue Ssa1 acts as a DNA‐binding transcriptional co‐activator of the fungal virulence factor, laccase, via binding to a GC‐rich element within the 5′‐UAS in response to glucose starvation, iron, copper, calcium and temperature. In addition, Ssa1 forms a regulatory complex with heat shock transcription factor and TATA‐binding protein during laccase induction. Furthermore, deletion of Ssa1 results in reduced laccase and attenuated virulence using a mouse model. These results indicate that Hsp70 functions as a stress‐related transcriptional co‐activator required for fungal virulence.