It is putting in place contingency plans to relocate funds and staff to England if what it sees as fundamental uncertainties about money and regulation are not sorted satisfactorily.
In its annual report, published today, Standard Life chairman Gerry Grimstone, says Scotland has been a great base for the company but that, "if anything were to threaten this, we will take whatever action we consider necessary - including transferring parts of our operations from Scotland - in order to ensure continuity and to protect the interests of our stakeholders".
According to Standard Life's chief executive, David Nish, the company, which has had its headquarters in Scotland for 189 years, has "started work to establish additional registered companies to operate outside Scotland, into which we could transfer parts of our operations if necessary. This is a precautionary measure to ensure continuity of our businesses' competitive position and to protect the interests of our stakeholders."
Standard Life is the UK's biggest provider of defined contribution pensions and self-invested pension plans, and has around £240bn of assets under management. It has 5,000 Scottish-based employees out of a total headcount of 8500 and 1.5 million shareholders.
The firm points to uncertainties about the currency to be used by an independent Scotland, how interest rates would be set, how financial companies like Standard Life would be regulated, how savings and pensions would be taxed, and on what timetable Scotland could join the EU.
Standard Life said it will "take whatever action we consider necessary" to ensure business continuity and to protect the interests of its stakeholders.
It has started work to establish additional registered companies to operate outside Scotland, into which it could transfer parts of its business.
Mr Nish said a number of material issues remain unresolved in connection with independence, including the currency that Scotland would use and the shape and role of its monetary system.
He also highlighted arrangements for financial services regulation and consumer protection and the approach to individual taxation, especially around savings and pensions.
Mr Nish added: "We will continue to seek clarity on these matters, but uncertainty is likely to remain. In view of this, there are steps we will take based on our analysis of the risks."
In annual results today, it reported operating profits of £751 million, a fall of 13% on a year earlier.
Deputy Prime Minister Nick Clegg said Standard Life's announcement "doesn't surprise me" because of uncertainty over issues such as currency and EU membership of an independent Scotland.
Mr Clegg told BBC Radio 5 Live: "Because of the failure of the SNP to prepare for this moment and spell out what they mean by independence, it is no wonder that major employers are saying 'Maybe we can't continue with our presence north of the border'."
Asked whether it was right for businesses to intervene in the independence debate, the Deputy Prime Minister said: "I think it's right for businesses to answer questions for themselves about their own business and address themselves to their own workforce, because there are thousands of people who work for Standard Life who want to know 'What does it mean for my future and my ability to pay my bills if Scotland were to be yanked out of the UK?'."
The Royal Bank of Scotland, which also reported annual results today, said it was "politically neutral" over Scottish independence, but warned a vote in favour could impact the group by affecting its credit rating.
It said: "The group's borrowing costs and its access to the debt capital markets and other sources of liquidity depend significantly on its and the UK Government's credit ratings, which would be likely to be negatively impacted by political events, such as an affirmative outcome of the referendum for the independence of Scotland."
The bank stressed it was "impossible" to quantify the financial hit of a Yes vote.
It added: "Clearly there are issues we are looking at - currency, the application of financial regulation, lender of last resort, credit ratings - which could affect us.
"But there is real uncertainty about how any of these matters would be settled in the event of a Yes vote and the outcome would depend on negotiations between the two governments."