It will be their first long-distance trek, but Mr Gerrard Lin and Mr Ng Junwei hope that for each of the 1,000km they complete, one person will sign up with the Bone Marrow Donor Programme.
The two 33-year-old men plan to take on the Bibbulmun Track from Albany on the south coast of Western Australia to Kalamunda in the Perth Hills. They aim to complete the route - which can take up to 12 weeks to finish - in just 20 days.
They also hope to raise $50,000 for the programme through donations.
It will not be the first time that Mr Lin, a fitness instructor dubbed "Ah Siao" for his "crazy" antics, will have gone the extra mile to rally support for the donor programme, which he has volunteered with for around eight years.
In 2012, he ran the Standard Chartered Marathon while pulling a 14kg tyre.
Two years later, he ran 31 marathons in 31 days in his March Marathon Madness campaign. That resulted in about 200 sign-ups - almost double the average number.
There are around 57,000 people on the registry, which is connected to an international database, yet there is only a one in 20,000 chance of a patient finding a match.
"This is a trip that is parallel to what a patient might go through," said Mr Lin, referring to the difficulties and unexpected challenges that might come their way. "After 20 days, even if we've suffered, we can go back to our lives. But what about that person waiting for a transplant?"
On average, the pair will trek 14 to 18 hours each day on a trail that will take them across beaches, swamps and forested areas. They have been training since January, when Mr Ng, a track-and-field coach, mooted the idea.
They meet three times a week for two to five hours each time - with a 10kg backpack on their shoulders - to run or climb staircases at places such as MacRitchie Reservoir and Mount Faber.
When Mr Lin first started 30km runs with the training pack, he said, his shoulders had a "stinging, needle-like pain."
But that has not stopped him from pressing on in his spare time.
He will take on the persona of "Ah Siao" on the walk, wearing a wizard's hat and a signboard explaining to strangers what the challenge is about.
"It's really not about the physical toughness or technical difficulty of it," said Mr Lin. "When you undergo a journey that is way beyond what you have done in your life, it is more about doing it from the heart."
Ms Jane Prior, chief executive of the Bone Marrow Donor Programme: "The value of 'Ah Siao' is that he's a challenging voice. When you meet the character out at an event, he's always berating people for not stepping up.
"If we can power him by getting a thousand new donors to sign up, that's a giant leap for the register - and that's another 1,000 chances to save a life."
• To find out more about the Bone Marrow Donor Programme, go to http://bmdp.org/be-a-donor