The Great Unconformity across the Proterozoic-Phanerozoic boundary records a significant change of the Earth's continents, atmosphere, environment and life. Its origin has been assumed to be glacioeustatic mechanism in the cratonic interior. On the contrary, we provide evidences for the sub-Cambrian Great Unconformity that can be traced across the Tarim Craton (NW China) from recent geochronological and seismic data. In the interior basement uplift, a distinct unconformity over an area of 300, 000 km2 presents a stratigraphic gap from the Paleoproterozoic (ca. 1.9 Ga) to the end Ediacaran. There is significant denudation beneath the Cambrian with compressional uplift. Given that the ca. 590–580 Ma Hankalchough diamictite (correlated with the Gaskiers glaciation) is absent in most areas, as much as 40 m.y. of stratigraphic gap constrained maximum span of the latest sub-Cambrian unconformity. The Precambrian uplift and denudation, and the age patterns of detrital zircon grains, overlap ca. 560–540 Ma advancing subduction process along the convergent southern margin of the Tarim Craton. This Great Unconformity may be linked to subduction-related uplift along the convergent southern Tarim margin, as occurred across peri-Gondwana. These relationships suggest tectonic driver rather than glaciation could lead to Great Unconformity in the cratonic interior as well as the continental margin