"Sport has the ability to reach people who may never walk through the door of a mental healthcare service," Prince William is expected to say at an event at Everton's football ground on Thursday.
"People who may never seek support themselves and may be struggling in silence," the prince will say later.
The On Your Side project wants to give people confidence to start the "difficult conversations" with friends, relations, teammates or colleagues who might be struggling with their mental health.
It aims to use the reach of sport to raise awareness about suicide and to show people the help available in a crisis, with the Football Association, Premier League and Team GB providing support.
Thursday's event will be Prince William's biggest public appearance in the UK since the return of the Duke and Duchess of Sussex.
Earlier this week, he attended the funeral of Norway's King Harald in Oslo and
The level of suicide is disproportionately higher among men than women - it's the biggest cause of death for men under the age of 50 in the UK.
"My hope is that every sporting organisation in the country will look at what is being launched today and ask a question: 'What more can we do? ' Because the opportunity before us is enormous," Prince William will say.
A film has been made, featuring England football captain Harry Kane and boxer Carl Frampton, talking about the importance of stepping in and offering help if people see someone who seems to be facing mental health problems.
Prince William helps to narrate the video, which aims to tackle the stigma around mental health and suicide, with 7,000 lives being lost to suicide each year in the UK.
The initiative has a practical toolkit, on a free website, for people who are worried or embarrassed about what to say to someone if they have concerns about their wellbeing.
It offers a sports-themed way of approaching the topic, called GOALS, representing G: get ready; O: open the conversation; A: ask the question; L: listen and respond and S: support and signpost.
Alan Shearer, former England football star and TV pundit, described it as "the first suicide prevention toolkit designed for the whole of UK sport".
"You don't have to be an expert. You don't have to have all the answers," said Shearer. "But we can all be better at asking, listening, and helping someone find the right support. "
Shearer said it was particularly poignant that the launch would be at Everton, one of the clubs where Gary Speed had played, a friend of Shearer's
The charity's founder Jake Mills said he had faced his own mental health challenges and saw sport as an effective route for this type of message.
He said sport was a "real force for good" in bringing people together and for "looking out for one another".
Mark Bullingham, chief executive of the Football Association, said he wanted to see sports organisations "creating a culture where conversations about well-being are really encouraged. Where people feel comfortable asking for help and also know where to get it".
Backing the project on Thursday in Liverpool will be former athlete Kelly Holmes, commentator Gabby Logan and former England footballer Jill Scott.
Prince William has been a longstanding campaigner over mental health and preventing suicide, with his Royal Foundation having last year launched the National Suicide Prevention Network.