The First Minister said around 30,000 young people leave the country every year, taking their skills elsewhere and dividing families.
He told the Business For Scotland annual dinner in Glasgow last night the situation "must change".
Addressing members of the pro-independence network, Mr Salmond said: "30,350 young people in Scotland - a record total - have been accepted into the colleges and universities of Scotland this year.
"What a fundamentally great thing that is for this country.
"The problem is not getting people into college and university, the problem is what happens after they graduate.
"What happens is that 30, 40, even 50% of them have to leave Scotland to pursue a career that befits the skills and human capital which they have acquired.
"If these people want to seek opportunity, they want to travel the world, that's fine by me. That is the joy of the 21st century.
"What I won't accept, what I think its intolerable, is that many of these 30,000 people leave Scotland not because they want to leave the country but because they have to leave this country to seek opportunities for which their skills have fitted them. That's what must change.
"Opponents say independence will divide families. What could be more divisive for families than 30,000 young people, trained, skilled, educated, leaving this country to seek opportunity elsewhere. That's what really divides families."
The First Minister told the audience at the Marriott Hotel: "Let us talk about how we make this country prosperous and just.
"We make it prosperous by raising our productivity to the best performing countries in Europe.
"Let us set ourselves to making sure that all of our workforce are available if they so choose to make their skills available to the labour market through a transformation in childcare.
"Let us set ourselves to valuing people's skills and achievements whether they are people who have come to be educated in our country or they are our own who are educated and then have to leave our country."
A Better Together spokesman said: "Nobody will trust a single word Alex Salmond has to say about our economy when he can't even tells us what currency we would be using in a separate Scotland.
"His failure to spell out a Plan B for what would replace the pound means Scots have no idea what their wages, pensions and benefits would be paid in.
"That's a risk we just don't have to take. We should say No Thanks to independence."