An image sensor module includes a substrate, a frame layer, a photosensitive chip, a transparent layer and a lens barrel. The substrate has a plurality of lead frame arranged in a matrix to form an upper surface, which is formed with a opening, and a lower surface, which is formed with a cavity penetrated from the opening. The frame layer is integrally formed with the substrate, and arranged at the periphery of the upper surface of the substrate to define a chamber together with the substrate, an internal thread being formed on the inner wall of the chamber. The photosensitive chip is mounted within the cavity of the substrate, and electrically coupled each of the lead frames in a flip chip manner. The transparent layer is covered onto the upper surface of the substrate to cover the opening. The lens barrel has a top surface, a bottom surface opposed to the top surface and a transparent region, a external thread formed between the top surface and the bottom surface, the lens barrel being arranged within the chamber of the frame layer, the external thread being screwed on the internal thread of the chamber.