The Reds slipped to a shock 2-0 loss at the Riverside on Saturday afternoon and were overtaken in second spot by Chelsea who secured a last-gasp 2-1 Stamford Bridge win over Wigan.
The Red Devils are now seven points clear at the top of the table with a game in hand and Benitez concedes it is almost all over for his side.
Benitez said after the Boro defeat: "Before the game, it was very difficult - after the game, it is more difficult. It depends on United. It will be more difficult, clearly."
On his side's performance, the Spaniard added: "I don't want to say too much, but for me, it is very clear. In the first 30 minutes, we had five chances and you have to take your chances.
"After the own goal, we still had chances. If you want to win, you have to score."