An image sensor module with a protection layer and a method for manufacturing the same includes a substrate with an upper surface and a lower surface, a chip is mounted on the upper surface of the substrate, a plurality of wires are electrically connected the bonding pads of the chip to the first electrodes of the substrate, a adhered layer is coated on the upper surface of the substrate, a lens holder has a lateral wall, a protection layer and internal thread, the lateral wall is adhered on the upper surface of the substrate by the adhered layer to encapsulate the chip, so that the protection layer is located on the sensor region of the chip to prevent adhered layer flowed to the sensor region of the chip; and a lens barrel is formed with external thread screwed on the internal thread of the lens holder.