In the present study, we showed that triptolide, an anti-cancer agent found to be effective against a variety of tumors in preclinical models [17–19] and now being tested in a Phase I clinical trial (https://clinicaltrials.gov/ct2/show/NCT01927965), is a potent inhibitor of HA-CD44/RHAMM signaling and associated oncogenes, including EGFR, Akt and ERK. This evidence concerns the gene HMMR and cancer.