Second seed Nishikori was unusually lethargic throughout the match, allowing Fognini to become the first unseeded player to make the Miami semi-finals since 2007.
It took the 29-year-old barely an hour to beat Nishikori in a match in which both players struggled on serve.
Fognini will play either Rafa Nadal or Jack Sock in the semi-finals.
(Reporting by Andrew Both in Cary, North Carolina; Editing by Greg Stutchbury)
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