The SNP leader used his annual address to say that if the tables of the upcoming 2014 independence referendum were turned, the outcome would be overwhelming.
Scots would not vote to give up independence and hand over powers in areas such as welfare or foreign affairs to London, he said in a recorded message.
Those advocating such a change would be pursuing "mission impossible" and would be "laughed at from Gretna Green to Dunnet Head," he added.
"This New Year the joke's on us – because that is exactly the position that we have in Scotland right now."
Mr Salmond adds: "This Scottish Government has a positive vision of the future of this country. We can build a new independent nation. It is a vision of a country that earns its wealth and shares it more fairly. A country confident in itself and its place in the world. A country which makes the most of its natural resources. And a country where everyone gets a fair shout and a decent chance."
The First Minister also used the address to insist that an independent Scotland could make a difference in areas such as foreign affairs.
He cited as an example of how Scotland can take a different path from the rest of the UK the decision to scrap the graduate endowment in 2007 restoring free university education.
His message was in contrast to that issued by David Cameron. The Prime Minister attempted to strike a positive note on the economy, saying that people could look forward to next year with optimism.
He also pledged a crackdown on welfare cheats, especially those who refused to work.
Mr Cameron said the UK was "heading in the right direction" and that, while recognising 2012 as "tough", people could look forward to the new year with "realism and optimism".
The First Minister faced a challenge from opposition parties in Scotland who insisted Scottish politics could not spend the next year obsessed with the constitutional question.
Scottish Labour leader Johann Lamont warned Scots could not "afford" such a focus.
"While politicians argue over the referendum, families all across Scotland are facing up to the harsh economic climate," she said as she also criticised the Tory-Liberal Democrat Coalition at Westminster, which she said had failed to deliver for Scotland over the past year.
"Opportunities for our young people are threatened, care for our elderly and vulnerable is squeezed and families are having to deal with rising bills in a time of unemployment, underemployment and pay freezes.
"Despite the claims of some, these problems will not be solved by re-configuring the constitution. But we can help people by arguing for a better way."
In his New Year's message Scottish LibDem leader Willie Rennie warned there needed to be more effort to tackle what he described as the new "great evils" of society.
These included a rapidly aging population, climate change and "the stubborn pervasiveness" of poverty, he said.
He added: "2012 has been a year when every issue, large or small, has been seen through the prism of the independence referendum. We can't afford to let this go on.
"The three evils facing us in the modern world must be confronted in their own right. The population is not going to get any younger, the ice won't stop melting or deprivation evaporate overnight no matter what the result in 2014."
Scottish Secretary Michael Moore defended the UK Government's record. He said: "People in Scotland, like the rest of the UK, place jobs and economic growth at the top of their priorities. We are well into the second decade of devolution and people expect their two governments to combine their efforts and ideas to create jobs and wealth."