Piranesi can only make sense of the grief he feels in response to the Other's death in terms of paradox:
My last thought before I fell asleep was: He is dead. My only friend. My only enemy.
At this point in the novel, Piranesi realizes that the Other is really Dr. Valentine Ketterley, a former disciple of Dr. Laurence Arne-Sayles who has trapped and imprisoned him in the House against his will. What's more, the Other attempted to shoot Piranesi and 16, even as they tried to save him from drowning in one of the House's floods. Despite this bitter betrayal, Piranesi still harbors feelings of warmth and affection toward the Other.
Thus, while it seems impossible that the same person could be both an enemy and a friend, this contradictory statement accurately captures how Piranesi feels. Even though he finally sees the truth about the House and the Other, it's hard for him to erase everything he thought he knew. In this way, paradox illustrates the complex double reality Piranesi inhabits. He is both Matthew Rose Sorensen, the man who despised Ketterley, and Piranesi, the man who depended on the Other for companionship and purpose. The word "only" is also significant—it shows how even though Piranesi knows he had a life before the House, its events are no longer significant to his sense of self and his perception of reality.