We present the intramolecular G-quadruplex structure of human telomeric DNA in physiologically relevant K+ solution. This G-quadruplex, whose (3 + 1) topology differs from folds reported previously in Na+ solution and in a K+-containing crystal, involves the following: one anti center dot syn center dot syn center dot syn and two syn, anti, anti, anti G-tetrads; one double-chain reversal and two edgewise loops; three G-tracts oriented in one direction and the fourth in the opposite direction. The topological characteristics of this (3 + 1) G-quadruplex scaffold should provide a unique platform for structure-based anticancer drug design targeted to human telomeric DNA.