The new 154-room hotel on James Street owned and operated by Sanguine Hospitality welcomes its first guests today.
The hotel occupies the five-storey former Ministry of Defence office, Moor House, above James Street station.
Days Inn Liverpool will operate as a three-star hotel and, said general manager, Paris D'Allessandro, has already secured £400,000 in bookings.
D'Allessandro added: "Days Inn Liverpool is in a prime location in the heart of the commercial district where there is already a great deal of improvement work underway."
Sanguine was established in 2007 by former Charlton Homes owner Paul Bolton and Simon Matthews-Williams, who brought the Crowne Plaza to Liverpool in the 1990s.