The invention provides a manufacturing method of flexible TFT substrate, forming first contact hole above two sides of the active layer and buffer hole on flexible base substrate after depositing a silicon oxide layer of interlayer dielectric layer (ILD), coating organic photo-resist material on the silicon oxide layer and filling the organic photo-resist material into the buffer hole during coating to form organic photo-resist layer to obtain ILD including silicon oxide layer and organic photo-resist layer, and patternizing organic photo-resist layer to form a connection hole corresponding to above of first contact hole so that the subsequent source/drain connected to active layer through the first contact holes and connection holes. By replacing the silicon nitride layer in conventional ILD with flexible organic photo-resist layer and providing buffer hole filled with organic photo-resist material on flexible base substrate, the flexibility of TFT substrate is enhanced and product performance improved.