However, it remains to be seen when building work will proceed, given the state of the property market.
Dublin City Council attached a series of conditions to its ruling, including a requirement that detailed drawings of the interface between the new buildings and existing structures be submitted for approval.
CIE has received permission to construct offices, 106 apartments and a hotel.
However, the company has said it would not go ahead unless the market improves.
It has been given a 10-year planning permission. CIE is expected to source private sector funding for the project.
It plans to demolish its central train control, maintenance shed and other office buildings.
These would be replaced by an 81,538sqm mixed-use commercial, community and residential development on a 3.2 hectare site.
In total, 13 new buildings, ranging in height from two to seven storeys, are to be built on an area currently occupied by offices and a car park.
Provision is also made for some 106 apartments, with three one-bedroom, 81 two-bedroom and 22 three-bedroom units, to be built in four blocks. A 110-bedroom hotel is planned for above Connolly Station. Seven blocks will take up over 50,000sqm of office space.
A new street through the site, linking Seville Place and Sheriff Street Lower, is also to be built. Provision for 550 underground car parking spaces, four coach spaces and 260 cycling bays are included in the plans.
CIE believes the site will be popular when there is an upturn in the property market. The National Transport Authority (NTA) supports the plan.
But the NTA stressed the need to provide a "high quality, safe and convenient pedestrian linkage" between the development site and the facilities offered by Connolly Station.
The Dublin Docklands Development Authority has also welcomed the plans.
But it said the proposal "does not have a readily identifiable civic open space, which could act as a focal point for the comprehensive redevelopment of the subject lands".