The 4-1 loss to Ajax ends a dreadful week for the Blancos, one which included a pair of Clasico losses to their fierce rivals.
Knowing that, many expect change to come for Real Madrid at the end of the season, and Nacho acknowledged that the run up until that point will be very difficult for the club.
"[It's] a turning point, because we have been eliminated from the Champions League and the Copa del Rey and we face a very difficult situation in La Liga," he said after the loss.
"The end of the season will be very difficult because we are not used to not playing for anything at this point."
After winning 2-1 on aggregate in the opening leg, Madrid capitulated en route to a 4-1 loss and a 5-3 aggregate defeat .
The loss was Madrid's worst home defeat in European competition in the club's history, and one that all but ended an era of dominance headlined by three consecutive Champions League crowns.
"It 's the worst night of the last few years," Nacho said. "We won many Champions Leagues and we are not used to not making it to the quarter-finals.
"I think that for many years did not happen, so it is is still a very difficult season for many reasons."
Still, the club faces 12 more matches in La Liga before the end of the season, and the defender, who was sent off late in the match, insists the players will continue to fight even if it is for nothing.
"We understand that the fans are upset with us, but we are locked in," he said.
"From within we live it very strongly. We noticed it, because we are people, we have been through bad things and this is a very hard one for us. "
Real Madrid face a trip to Real Valladolid for the club's next Liga match on Sunday.