News Corporation launched the iPad-only title, conceived for the Apple iPad, back in early 2011 in the US.
The Daily is aimed at a younger audience than traditional newspapers. It publishes more than 100 pages of daily content, including news, sport and comment.
At the time of launch, Murdoch believed The Daily could revolutionise the newspaper model.
News Corporation said the staff cuts would "enable the business to operate more efficiently and with even greater focus on the types of content that had consumers have gravitated towards since launch."
It is cutting 50 full-time staff based in the US from an overall headcount of 170.
The job cuts are thought to predominantly hit the publication's sports and opinion sections.
Jesse Angelo, The Daily's editor-in-chief Jesse Angelo informed staff of the cuts this week.
The News Corporation-owned title has previously denied reports that it had considering closing the title down.
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