Top seed Rafael Nadal defeated fifth seed Pablo Cuevas 6-3, 6-2 on Friday to set up a Hamburg semi-final clash against Italian veteran Andreas Seppi.
Nadal, 29, broke the Cuevas serve five times on his way to a second triumph over the Uruguayan this year, having also beaten the South American in the Rio de Janeiro quarter-finals in February.
Nadal is playing in Hamburg for the first time since 2008, when he lifted the trophy with victory over Roger Federer, as the left-hander looks to breathe life back into his flagging season.
Seppi, who knocked Federer out of the Australian Open this year, enjoyed a walkover into Saturday’s semi-finals when compatriot Simone Bolelli withdrew due to gastroenteritis.
Seppi trails Nadal 5-1 in career clashes with his only win coming in 2008 in Rotterdam.
The other semi-final sees French qualifier Lucas Pouille face Italy’s Fabio Fognini.
World number 85 Pouille defeated countryman Benoit Paire, who was champion on clay at Bastad last weekend, 6-3, 6-2.
Eighth seed Fognini beat Britain’s Aljaz Bedene 6-4, 7-5.