The present disclosure provides a pixel structure and a fabrication method thereof, a display substrate and a display apparatus. The pixel structure includes a plurality of first pixel portions arranged in a plurality of rows and a plurality of columns, and a second pixel portion that spaces the plurality of first pixel portions from each other. Each first pixel portion includes a plurality of first sub-pixels having a same color and arranged around a center of the first pixel portion. The second pixel portion includes a plurality of second sub-pixels. For four first pixel portions in two adjacent rows and two adjacent columns, each of four regions that are centrosymmetric and obtained by connecting centers of the four first pixel portions to each other corresponds to one pixel unit, and each pixel unit includes two first sub-pixels respectively in two first pixel portions and at least one second sub-pixel.