The Japan international, who joined the Rossoneri from CSKA Moscow in January, scored his side's second goal of the night in the 56th minute when he ran at the Rossoblu defence before chipping over an advancing Mattia Perin.
The goal succeeded Adel Taarabt's 20th-minute opener which came in similar circumstances although the Moroccan was able to fire his shot low rather than take the aerial route.
An own-goal from Milan keeper Christian Abbiati with less than 20 minutes remaining gave Genoa hope but in the end, Clarence Seedorf's men got the job done to record their third league win in a row, to move up to 11th on Italy's top flight table.
Since arriving at the San Siro, Honda has played 12 times in Serie A whilst also making two Coppa Italia appearances for one goal on debut back on January 15.
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