"It's absolutely thrilling, but it is a load, it is a responsibility. You have this vast machine of about 250 people, 250 working parts, and they're all looking for answers and direction and purpose," he said.
"I suppose it should make me more sympathetic to other directors, but it probably won't."
Laurie teased that the structure of the episode is "unusual", with two separate stories happening in parallel, one within the show's normal setting and the other "away from the hospital, between [House] and Wilson".
In the most recent episode, Wilson (Robert Sean Leonard) revealed to House (Laurie) that he has stage 2 cancer, and the next instalment will see the pair react to his diagnosis.
"This episode I've been given contains an immensely powerful storyline for the character of Wilson," Laurie commented. "I feel a tremendous responsibility to do him justice, to do Robert as an actor justice, and also the character."
He went on to joke about his fellow actors' reaction to his direction, saying: "I realise it must be a bit odd for them.
"Whether or not they go out round the back and start bitching about me as soon as my back's turned, I don't know.
"If they are, they're hiding it well, and that's all I ask. Just hide it well."