The 60-year-old was using a forklift to transport the drywall in the store in St. Peters on Tuesday just after 12:15 a.m. when multiple sheets fell and struck him on the head, St. Peters Public Information Officer Melissa Doss said in a statement.
The victim, who was not identified, was transported to a local hospital, where he was pronounced dead, Doss said.
Coworkers on the scene confirmed to police that the man was an employee, Doss said.
Home Depot said in a statement to ABC News that they are "deeply saddened by this tragic accident."
"We immediately contacted the proper authorities, including OSHA, and are cooperating with their investigation," the statement read.