Saturday's Premier League fixture at Chelsea sees Wenger take charge of Arsenal for the 1,000th time as the Frenchman approaches the 18th anniversary of his appointment.
In that time, Arsenal have won three league titles and the FA Cup four times, as well as reaching the final in both of Europe's major competitions.
Former chairman Hill-Wood, having seen the difficult transition Manchester United are going through after losing Alex Ferguson, feels it will be an almost impossible task to replace the Frenchman in the future.
"I will be extremely difficult," he told The Daily Star. "I dread to think who is coming in.
"If we were to lose Arsene it would be a nightmare.
"There is nothing obvious. I am sure Arsene will have some input.
"He has an enormous amount of knowledge and has developed a lot of really excellent players who, overall, weren't that distinguished when they came to us.
"Many of them became household names at Arsenal. Thierry Henry is a very good example, also Cesc Fabregas, Patrick Vieira and Robin van Persie."
Wenger is out of contract at the end of the season, but Hill-Wood assured fans there was nothing to worry about.
"I have spoken to (chief executive) Ivan Gazidis and he is very confident that there isn't a problem," he said.
"It's just that he doesn't want to sign up right now, that's all. It's not a question of somebody dangling greater riches in front of him.
"I don't think his enthusiasm has diminished at all. He doesn't think his job is finished yet."
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