The shooting happened after an employee at Atlantis Plastics had an argument with a supervisor, Henderson police Lt. David Piller said.
In addition to the four deaths, Piller said two others, who were injured, were flown to hospitals in Evansville, Ind.
The employee used a handgun he retrieved during a break, Piller said.
The shooting victims were scattered around the plant, Piller said.
"It appears the shooting was random at this time," Piller said.
Police did not say if the supervisor the employee argued with was among the victims.
A woman who answered the phone at a number for Atlantis Plastics declined to give her name and would only say that the company would not comment until a 3 p.m. news conference.
Names of those involved in the shooting have not been released.
Hours after the shooting, police had set up a roadblock on the street leading to the plant, which is in an industrial area on the southern side of Henderson.
Other employees at the plant were sent home.
In a news release on the company's Web site, Atlantis Plastics says it is a leading U.S. manufacturer of three kinds of products: polyethylene stretch films for wrapping pallets of materials, custom films for industrial and packaging uses, and molded plastic pieces used in products such as appliances and recreational vehicles.
The company has 700 employees, including 200 in Henderson, and annual sales of $110 million, according to business directory Hoovers.
