The present invention discloses an image sensor package structure with a large air cavity. The image sensor package structure includes a substrate, a chip, a cover and a package material. The chip is combined with the substrate. A plastic sheet of the cover is adhered to the chip and a transparent lid of the cover is combined with the plastic sheet to provide a covering over a sensitization area of the chip so as to form an air cavity. The package material is arranged on the substrate and encapsulated around the chip and the cover. The plastic sheet having a predetermined thickness can increase the distance between the transparent lid and the chip to enlarge the air cavity. Thus, the image-sensing effect of the image sensor package structure can be improved and the ghost image problem resulting from multi-refraction and multi-reflection of light can be minimized.