Kevin Anderson's Delray Beach Open campaign came to an abrupt end on Wednesday after the top-seeded South African was upset in straight sets by Lu Yen-Hsun.
A day after second seed John Isner was eliminated, Chinese Taipei's Lu - ranked 61st in the world - stunned Anderson 7-6 (7-5) 6-3 in one hour, 18 minutes at the ATP 250 event.
Lu's first serve proved the difference in the second-round clash, with the 2010 Wimbledon quarter-finalist enjoying a 90 per cent success rate on his first serve, while only dropping 12 points on serve.
After claiming the first-set tie-break, Lu and Anderson exchanged service breaks at the start of the second.
The decisive break came in the sixth game as Lu broke Anderson for a 4-2 lead, which he never relinquished en route to setting up a quarter-final showdown with fifth seed Adrian Mannarino.
"He's a great player, and you cannot give him any chances," said Lu. "All the match I was really concentrating … this match has made me get a little bit of confidence back for the year."
Frenchman Mannarino accounted for American wildcard Denis Kudla 6-2 6-2 in just 59 minutes on court.
"It was a good thing for me that the conditions were very cold and pretty slow because I was able to move very well on the court, and Denis was missing a little bit more than me," Mannarino said.
"I was concentrating on winning one match. Yesterday, I was really happy after my match, and I was like, let's continue in the next match. I was able to win one more, and I'm just going to take it match after match."
Fellow seeds Ivo Karlovic and Steve Johnson will meet in the quarters after respective wins on Wednesday.
Karlovic - the Croatian fourth seed - required two tie-breaks to overcome Australian qualifier Thanasi Kokkinakis 7-6 (7-4) 7-6 (7-2).
American seventh seed Johnson, meanwhile, saw off Andrey Rublev 6-3 6-3 after converting on five of his seven break points against the Russian wildcard.