Lake Ellsworth lies below ice that is at least two miles (3.2km) thick.
Its pitch-black waters have remained isolated and unseen for up to half a million years.
This will be the first attempt to extract uncontaminated samples of water and sediment from a body of water so far below the surface. Earlier this year, a Russian expedition drilled and breached Lake Vostok, on the other side of the continent. That venture yielded clues as to the prevailing conditions beneath the permafrost.
The investigation is part of a search to understand the limits of where life is possible and, despite the high pressures and lack of sunlight, it is likely that microbes will be detected.