The derelict site on West India Dock Road will be transformed into a 400-bedroom hotel and 66 private residential units.
The scheme will also include a restaurant and café, gym facilities and a landscaped pocket park. Construction will begin this Autumn.
The Sisk UK South business has a strong track record in the region building hotels, offices and residential developments.
Ajaz Shafi, Regional Managing Director at John Sisk & Son, said: “We are delighted to have been appointed by Rockwell to deliver this important landmark scheme in the heart of East London.
“We look forward to working in partnership with all our stakeholders and in particular the local community to create a lasting legacy.
“We deliver quality projects by using innovative construction techniques and digital technology to plan, design and build, with a focus on safety.”
Donal Mulryan, Founder of Rockwell, said: “We are delighted to confirm the pre-construction services appointment of John Sisk & Son for the construction of this landmark development in Canary Wharf.
“Their track record and experience will help us to deliver this significant mixed use scheme which will bring new jobs and businesses to the local area, in addition to much needed homes for the local community.
“We are immensely proud of this development and look forward to seeing our vision become a reality.”