Roger Federer of Switzerland reacts during his quarter-final round match against Tomas Berdych of the Czech Republic at he 2011 Cincinnati Open tennis tournament in Cincinnati, Ohio, August 19, 2011.  [Photo/Agencies]

MASON, Ohio - Rafa Nadal and Roger Federer, numbers two and three in the world, suffered surprise defeats to inspired opponents in an entertaining quarter-finals day at the Cincinnati Open on Friday.

To the delight of a packed home crowd, American hard court specialist Mardy Fish beat Nadal for the first time in his career, 6-3 6-4, to book a spot in the semi-finals where he will face Britain's Andy Murray.

Then Federer was undone 6-2 7-6 (3) by Czech Tomas Berdych, who after beating him twice last year is becoming something of a bogeyman for the Swiss.

Fish entered the match having lost his prior six meetings with the Spaniard but battled hard against Nadal, who, troubled by his burnt fingers and foot blisters, struggled against his opponent's serve.

Nadal handed Fish the advantage in the first set with a double-fault on break point, and the American played on with greater confidence.

The seventh-seeded Fish, who produced 12 aces, made the decisive break to go up 3-2 in the second set when Nadal went long on a return.

After having the bandage on his foot changed, Nadal found some extra power as he fought in vain to break back.

Spain's Rafael Nadal reacts during his quarter-final round match against Mardy Fish of the U.S. at the 2011 Cincinnati Open tennis tournament in Cincinnati, Ohio, August 19, 2011.  [Photo/Agencies]

But Fish's powerful serve was on display in the final game when he served to love for the match.

Nadal, who burnt his fingers on a hot plate at a local restaurant earlier in the week, had played a three and half hour, three-setter against Fernando Verdasco on Thursday and then kept his doubles commitment.

But he said his game had simply not been at its best.

"I didn't play well. It was a bit of an unlucky week for me with the burned fingers and the very long match yesterday. There is no excuse though -- the only excuse is that he played better than me," he said.

Fish, who lost to Nadal at Wimbledon, said this match had felt different from the outset.

"There is that difference between the feeling that you can win or even that you should win rather than that you hope to win," he said.

The centre court crowd then watched another surprise as Berdych delivered a reminder of his quality.

Federer, who had won 24 of his previous 26 games in Cincinnati, never got to grips with Berdych's powerful serve as he suffered another setback following a third-round exit in Montreal last week.

Murray enjoyed a comfortable 6-3 6-3 win over France's Gilles Simon in his quarter-final.

The Scot, who has won the last seven meetings with 10th seed Simon, exchanged breaks with his opponent to start the match but was in control the rest of the way.

Simon was the only player outside the top eight seeds to reach the quarter-finals after a three-set win over Spain's David Ferrer Thursday that lasted over three hours.

World number one Novak Djokovic is in action later Friday against France's Gael Monfils, with the winner facing Berdych.