El Reno is located about 30 miles west of Oklahoma City.
Severe weather also struck Green County, Oklahoma, on Saturday, and a tornado caused damage and injuries in Sapulpa just after midnight.
The American Budget Value Inn in El Reno suffered extensive damage, as the tornado ripped off the motel's second floor, KFOR reported.
"As far as we know right now, there is no one in the rubble," the hotel's owner, Ramesh Patel, KOCO.
The woman who was working in the motel's office broke her leg, Patel told ABC News.
Officials said multiple mobile homes were flipped at the Sky View Mobile Home Park, which is near the motel, according to KFOR.
Tweedy Garrison, a resident at the mobile home park, said she gathered her grandchildren into the kitchen when the tornado hit.
"We had debris coming down on top of us, knocked us all down. There was no way we could have gotten out without help," Garrison told KFOR.
"I had 2% on my phone. (My son’s) name showed up (on caller ID) and I hit the button, told him that we got hit, the boys are fine. And within five minutes, he was there.”
The tornado comes after a very busy and severe weather week. According to ABC News, since Monday 104 tornadoes have been reported across eight states, including Oklahoma, Missouri, Kansas, Texas, Nebraska, Iowa, Illinois and Maryland.
"We have absolutely experienced a traumatic event here in El Reno," Mayor Matt White told ABC News. "None of this is easy, we're all shook up."