Goals from Joris Mathijsen and Ruud van Nistelrooy put the Bundesliga side two up before Jonathan Legear curled home a glorious free-kick in first-half stoppage time for the Belgians.
But David Jarolim guided a volley into the bottom corner from the edge of the area in the 67th minute to restore Hamburg's two-goal advantage as they ran out 3-1 winners.
Wolfsburg have the upper hand in their tie with Rubin Kazan after drawing the first leg in Russia 1-1.
Zvjezdan Misimovic equalised in the 67th minute to cancel out Cristian Noboa's opener just before the half-hour mark.
Atletico Madrid and Sporting Lisbon drew 0-0 in the Spanish capital.
The visitors played for most of the game with 10 men following the 31st-minute sending off of Leandro Grimi for two yellow cards.
However, that wasn't their only disciplinary problem as they were reduced to nine in the 89th minute when Tonel received a straight red.
Standard Liege enjoyed perhaps the most impressive win of the night with a 3-1 success against Panathinaikos, who beat Roma in the last round, in Greece.
Goals from Axel Witsel and Milan Jovanovic put the Belgians two up in the opening 16 minutes.
Loukas Vyntra pulled one back three minutes after the break, but Igor De Camargo added a third for the visitors in the 74th minute and Pana's miserable night was complete when Simao was sent off in the 90th minute.
Second-half substitute Hatem Ben Arfa headed a 90th-minute away goal to earn Marseille a 1-1 draw at Benfica.
Ben Arfa, who came off the bench in the 74th minute, cancelled out Maxi Pereira's 77th-minute opener.
Juan Mata equalised for Valencia two minutes after they had been reduced to 10 men to earn a 1-1 draw at home to Werder Bremen.
Torsten Frings put the Germans ahead with a 25th-minute penalty and the visitors received another boost when Ever Banega was sent off 10 minutes after the break.
But Mata levelled to give the La Liga side hope going
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