The cold waters of Lake Ellsworth -- 9 miles long, nearly 2 miles wide and 525 feet deep -- have remained in the dark for up to half a million years, they said.
Scientists say they hope a study of the ice-covered lake will help them understand the limits of where life is possible.
Despite the high pressure of the lake's water and the absolute absence of sunlight, they said they believe it likely that microbes, at least, will be discovered.
The $13 million project will use a hot-water drill to open a hole from the surface of the ice sheet all the way down to the lake.
A challenge for the researchers is that all the equipment used has to be kept sterile throughout the process, so as not to contaminate any samples from the lake water.
"The first challenge was to develop the equipment and we've done that," project chief scientist Martin Seigert of Bristol university said. "The second was to keep it clean and we've done that. The third was to get it to Antarctica in a clean way and we've done that too."
The drill hose, all 2.6 miles of it, has been cleaned and checked, he said.
"Now the experiment is set we can hit the Go button."