Meanwhile, Ajax Amsterdam suffered their first defeat of the season against Vitesse Arnhem on Saturday.
Heracles, who were unbeaten in seven matches, fell behind after 19 minutes when Dries Mertens curled home and Luciano Narsingh doubled the advantage from close range nine minutes before the break.
Kevin Strootman added a third before Heracles' Kwame Quansah was sent off for a second booking and the hosts' Tim Matavz completed the rout.
PSV are top with 27 points, two ahead of Twente Enschede, who host fifth placed Feyenoord on Sunday.
Vitesse remain third with 24 points after they registered their first win at Ajax in 11 years, beating the defending champions 2-0.
Ajax, who had drawn their last three league matches, fell behind seven minutes before the interval when Ivorian Wilfried Bony collected a deflected cross and finished from 15 metres.
Bony settled the match a minute after the restart when he headed home a fine cross from winger Renato Ibarra.
Jacob Mulenga and Alexander Gerndt both scored twice as Utrecht won 5-1 win at second-bottom Willem II Tilburg to go fourth with 21 points.