Foreign Secretary William Hague, in a speech in Glasgow, said Scotland is financially better off, more secure and has more influence in the world as part of the UK.
He launched the latest Scotland Analysis paper, on the EU and international issues, which puts forward arguments for a No vote in the referendum in September.
He said Scotland would have to join a queue to be part of the EU and then have to negotiate separate terms of entry, which would be less favourable than under the present UK deal.
Mr Hague said Scotland would not benefit from the EU budget rebate the UK gets which would lead to Scotland paying a greater share of the budget than it does now.
Figures in the report said that it is estimated Scotland would contribute €12.9 billion to the EU budget over the next six years.
That, he said, is €2.9bn more than under the UK deal, working out at an extra €1100 per household. That is £908 if converted to the current exchange rate.
The report states: "Scotland would lose out financially in EU funding as an independent member state of the EU. It would receive less in structural funds during 2014-20 and lose the benefit of the UK's rebate.
" Scotland would, instead, have to contribute to the UK's rebate like other member states. Scotland's taxpayers would pay significantly more to the EU than they do now."
Mr Hague claims by the SNP that a newly-independent Scotland would join the EU could not be guaranteed.
He added: "It is indisputable Scotland outside the UK would find itself less connected and less able to influence decisions in a shifting international order. EU membership is unlikely to be as easy as the Scottish Government makes out."
Mr Hague was joined by Danny Alexander, Chief Secretary to the Treasury, who said it was unlikely Scotland would be able to get a budget rebate deal. He said: "No other country has ever secured a budget correction (rebate) in joining the EU."
Deputy First Minister Nicola Sturgeon said: "He is an example of the same old hypocritical Tories lecturing Scotland on why we shouldn't be taking decisions ourselves.
"Let's remember he is the Tory politician who came to Scotland before devolution to scaremonger over what would happen if the Scottish Parliament was set up. He was wrong then and he is wrong now.
"He's campaigning for an in/out referendum which could see Scotland out of the EU even if we vote to stay in."