The invention provides a multi-dimensional liquid chromatography separation system, comprising a high performance liquid chromatography gradient pump A, a high performance liquid chromatography gradient pump B, a high performance liquid dilution pump, a gradient mixer A, a gradient mixer B, a sampling valve, an enriching column array A, an enriching column array B, a fraction collector, a liquid chromatographic separation column array, a detector, a two-position ten-way valve and a connecting pipeline, wherein the two-position ten-way valve switches to realize the transformation between the last-dimensional separation state and the next-dimensional separation state, so as to realize three or more-dimensional chromatographic separation. Respective-dimensional chromatographic separation columns are selected through the liquid chromatography separation column array, thereby, based on the same gradient elution system and the same detector, realizing the full-line monitoring and control ofthe multi-dimensional chromatographic separation, and realizing the controllability of cleanliness degree of the enrichment column and the separation column. Respective-dimensional separations are connected by the enrichment column, and the liquid dilution pump is used to assist in compound enrichment or capture. The system achieves efficient separation of monomer compounds in complex system samples with high separation difficulty by selecting different combinations of chromatographic stationary phases and mobile phases.