Second-placed Boro are breathing down the necks of leaders Coventry after a fourth consecutive win saw them open up a five-point lead over the chasing pack.
Alan Browne opened the scoring against his former club before Tommy Conway and Morgan Whittaker put the home side 3-0 up by half-time.
Preston's Jordan Storey was red-carded shortly after the resumption before Conway rounded off the scoring.
"Of course I watch the table, but we need to keep our performance up," said Middlesbrough boss Kim Hellberg.
"It's not for me to focus too much on the table because I need to prepare my team and develop them."
Coventry's lead at the top is now down to three points prior to their trip to Norwich on Monday.
Third-placed Ipswich failed to keep pace with Middlesbrough after their seven-game unbeaten run was ended by a 3-1 defeat at Sheffield United.
Callum O'Hare, Andre Brooks and Patrick Bamford netted for the Blades to pull Chris Wilder's side six points clear of the relegation zone.
Wrexham are making a charge for a remarkable fourth consecutive promotion as the Welsh side, co-owned by actors Ryan Reynolds and Rob McElhenney, moved into the top six.
Wrexham trailed twice at Loftus Road, but two goals in stoppage time from Josh Windass and Oliver Rathbone secured their fifth win in eight games.
Hull moved level on points with Ipswich with a 2-1 win over Swansea to maintain their unexpected promotion push.
Millwall are just one point further back after they thrashed Charlton 4-0 in a south London derby.
Oscar winners Daniel Day-Lewis and Gary Oldman were in attendance at The Den to see Caleb Taylor, Luke Cundle and Aidomo Emakhu strike for the Lions after Kayne Ramsay's early own goal.
Oxford remain second-from-bottom but are just two points adrift of safety thanks to a 2-1 win over Leicester at the King Power Stadium.
Bristol City are just one point outside the play-off places after a 2-0 win over bottom-of-the-table Sheffield Wednesday.