Image sensor package structure and method are provided. The method includes: providing first substrate having upper surface on which image sensing areas and pads are formed; providing second substrate having through holes; forming tape film on upper surface of second substrate to seal each through hole; contacting lower surface of second substrate with upper surface of first substrate to make image sensing areas in through holes; removing portions of tape film and second substrate, wherein remained tape film and second substrate form cavities including sidewalls made of second substrate and caps sealing sidewalls and made of tape film, and remained second substrate also covers pads; removing portions of remained second substrate to expose pads; slicing first substrate to form single image sensor chips including image sensing areas and pads; and electrically connecting pads with circuits on third substrate through wires. Pollution or damage to image sensing areas may be avoided.