Osborne unveiled plans to make £6.2bn worth of cuts as part of "urgent action" to address the UK's budget deficit - estimated to be around £156bn.
BIS, headed up by Vince Cable, will bear the brunt of the cuts after it was told to find £836m in savings over the next nine months.
This is in comparison to £683m at the Department of Transport, £780m in Communities and Local Government and £670m in Education.
Osborne said: "We simply cannot afford to increase public debt at the rate of £3bn each week. Our huge public debts threatened financial stability and if left unchecked would derail the economic recovery.
"Public borrowing is only taxation deferred and it would be deeply irresponsible to continue to accumulate vast debts that would have to be paid off by our children, and our grandchildren, for many decades to come."
Despite having to find the £836m savings, Vince Cable's department will receive about £200m of "recycled efficiency savings", which Osborne said could be used for apprenticeship schemes, support for further education colleges and a backdated freeze in business rates.
Today's announcement comes ahead of Osborne's emergency Budget, to be held on 22 June. Further details of the cuts are expected to follow.
Liam Byrne, Labour's chief secretary to the Treasury before the coalition was formed, said the new government had "embarked on the wrong way" to tackling the deficit.
In addition, trade union leaders are gearing up for a fight with Brendan Barber, general secretary of the Trades Union Congress, warning that the cuts were "dangerous" and put the country at risk of a "double-dip recession".
BIS one of the biggest losers in Osborne's spending cuts
Business, Innovation and Skills (BIS) is set to be one of the hardest-hit departments under newly announced spending cuts by chancellor George Osborne today (24 May).