Since denying O'Sullivan the chance to win his sixth world title in 2014 with an 18-14 win in Sheffield, O'Sullivan has never been back to the final while Selby has progressed to win twice more at the game's blue-chip event with victories over Ding Junhui (18-14) and John Higgins (18-15) over the past two years.
Leicester's Selby enters the event having lifted the China Open with a 11-3 win over Barry Hawkins in Beijing last Sunday. He starts the tournament a week on Saturday as the game's undisputed number one.
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But world number two O'Sullivan is enjoying the best season of his career having won five titles and made 70 century breaks. He is number one in the world on the one-year list, and will become the first man to surpass £1m in prize money in a season if he can win the £425,000 winner's cheque.
There is the tantalising prospect of a best-of-35 frames final between the game's two top players on May 7.
"Of course I can win, I’m one of 10 players who can win it," said O'Sullivan.
"But like I said, until the tournament starts. Until you get into it, you never really quite know what’s going to happen. The first round is a difficult one because it’s the first one. But once you get going and you get in your stride anything is possible.
I think Mark Selby is obviously (the favourite). He’s won it three times out of the last four. Great match player. If he gets it right every player in the tournament knows he’s a proper handful. And obviously Judd Trump as well. If he gets it right he’s a handful for anybody.
"He’s a very different player to Selby and John Higgins. I love watching John Higgins, he’s the ultimate player. And I love watching Judd Trump play because he plays snooker in a way nobody else plays.
O'Sullivan feels Higgins, Judd Trump, Ding Junhui and Mark Williams are also worth watching in the endurance race of this year's 17-day event in Sheffield.
"I think obviously Selby, John Higgins, I think Mark Williams is playing very well," said O'Sullivan. "Ding Junhui has had some good results there the last few years. But like you say, snooker is so wide open today.
There are so many players capable of winning tournaments. It could be anyone of seven, eight or ten people who could win this year’s WC. It’s just another tournament that happens to be the WC. So there are no guarantees of who could be picking up that trophy.
At the age of 42, O'Sullivan would be the oldest champion since Welsh icon Ray Reardon lifted the world title at the age of 45 in 1978.
A victory for the sport's biggest name would be hugely popular, and would see him equal Steve Davis' and Reardon's haul of six. It would leave him one behind Stephen Hendry's modern record of seven.
O'Sullivan feels he is fit enough to last the pace after a season that has seen him win the UK title, Shanghai Masters, English Open, World Grand Prix and Players Championship.
"There’s load in the tank. I haven’t exerted much at all, obviously other than having to go through winning tournaments," said O'Sullivan.
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"That’s the easy part I think, the in between part, I don’t do too much practice. I do enough just to get me on the starting line and I spend a lot of time with my family and my friends.
"I’m really enjoying life you know. I feel like I have a really good balance. For me, if something gets a bit too hard then it’s not for me.
So like I said, there’s been two or three times throughout the season where I knew I had played too much and I knew losing early in the tournament was the best thing that could happen to me. You lose early, have a few days off, recover for the next tournament.
"Trying to go deep in every tournament you’re just going to leave yourself feeling shattered. I think at this stage of my career, you want to preserve yourself as much as you can."
Watch the World Championship on Eurosport and Eurosport Player starting on April 21 until May 7.
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