The invention discloses a regional-level power grid operation regulation method based on 0-1 nonlinear integer programming. The method comprises the steps of (S1) setting the number of 220kV substations to be N1, the number of 110kV substations to be N2, and the number of 110kV virtual substations to be N3, wherein N1+N2+N3=N, Kij represents a connection branch of a node i and a node j, 0 is no connection, 1 is connection, Kii = 0 (i = 1, 2 to N), an N*N adjacency matrix A can be obtained from the grid information, the adjacency matrix A is a symmetric matrix, and a power supply path of a substation can be searched by using the matrix, (S2) inputting the number N1 of the 220kV substations and the number N2 of the 110kV substations, searching a 110kV substation node branch by using a depth-first search algorithm, marking the branch and continuing to search if a search node is not a 220kV substation node until the 220kV substation node is searched; and (S3) saving a search result and returning to search other branches of a previous node along an original search path and repeating continuously.