Embodiments of the present disclosure provide a touch display substrate and manufacturing method thereof. The method includes forming a touch signal line on a base substrate through patterning process; depositing a photoresist layer, and forming a first thickness photoresist layer, a second thickness photoresist layer and a photoresist layer opening area through patterning process, the touch signal line being located in the photoresist layer opening area; depositing a first insulating layer on the photoresist layer, the first insulating layer comprising a first area and a second area, wherein the first area is located on the first thickness photoresist layer, the second area is located on the second thickness photoresist layer and the photoresist layer opening area, the first area and the second area of the first insulating layer are disconnected; removing the photoresist layer and the first insulating layer located on the photoresist layer; and depositing a second insulating layer.