The invention relates to a karst region underground river blocking structure and method, and belongs to the technical field of water conservancy and hydropower engineering. The structure comprises drain holes, mold bag grouting holes, steel pipe piles, concrete grouting holes and dense grouting holes. According to a specific implementation scheme, a row of steel pipe piles are arranged on the upstream and the downstream of a curtain line respectively; the drain holes are formed in the upstream of the upstream steel pipe piles for drainage and pressure reduction; the mold bag grouting holes areformed in the inner sides of the upstream steel pipe piles and the downstream steel pipe piles; mold bags are poured into the mold bag grouting holes; concrete or mortar is poured into the concrete grouting holes; cement paste is used to block the drain holes; and finally water pressing test inspection is conducted. The karst region underground river blocking structure and method have the advantages of easy construction, saving of a large amount of pore-forming footage and various grouting footage, reduction of use of grouting materials, investment saving, protection of the underground environment, and shortening of a construction period.