Hamilton powered past their SPL opponents to progress to the quarter-finals of the CIS Cup for the first time since 1981.
Teenager James McCarthy gave the First Divsion side the lead after 16 minutes as Kilmarnock struggled to keep Accies' attacks at bay.
As Killie battled to get back into the game James McArthur doubled Hamilton's lead eight minutes before the break.
The First Division leaders held firm in the second half to secure victory.
Kilmarnock's defence was under the cosh from early in the game and lost the opening goal when David Winters' cross broke to McCarthy who slid the ball home.
The SPL side's Colin Nish then fed Grant Murray, but his header was superbly saved by goalkeeper Bryn Halliwell.
McArthur doubled Accies' advantage after 37 minutes.
Lilley tried to clear a Mark Gilhaney cross only for the ball to unintentionally come off his hand.
Claims for a penalty were ignored by referee Kenny Clark but the ball broke kindly to McArthur who sent a right-footed shot low into the back of the net.
Kilmarnock tried in vain to reduce the deficit and Jim Jefferies' side's misery was compounded when David Fernandez received his marching orders after two quick yellow cards.
Hamilton: Halliwell, Parratt, Gibson, Elebert, Swailes, Winters, McCarthy (Easton 84), McArthur, Stevenson, Gilhaney, Offiong (Wake 77). Subs Not Used: Cerny, McLeod, Crawford.
Goals: McCarthy 16, McArthur 37.
Kilmarnock: Combe, Murray, Lilley, Ford, Wright, Dodds (Flannigan 8), Fowler, Johnston (Jarvis 46), Gibson, Nish, Bryson (Fernandez 45). Subs Not Used: Rascle, Hamill.
Sent Off: Fernandez (78).
Booked: Lilley, Wright.
Att: 2,627
Ref: K Clark
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