Two-dimensional conjugated metal-organic frameworks (2D c-MOFs) have emerged as an intriguing class of quantum materials due to their high crystallinity, persistent spin centers, and tunable structures and topologies. However, it remains unclear how to achieve long spin relaxation time at room temperature in 2D c-MOFs via a bottom-up design strategy. Herein, we design a hexahydroxytrithiatruxene ligand (HHTH) to minimize the influence of nuclear spin on electron spin relaxation while weakening