In order to overcome the shortcoming of the conventional optical focusing method, such as unable to detect on the patterned area, photoetching material′s potential exposure, complicated laser path and low sensitivity, method of using high sensitivity pneumatic micro-distance measurement system for lithography autofocus is investigated. The principle, design, method and error analysis are introduced. The pneumatic micro-distance sensor can detect the varity of air flow to determine the defocusing amount. The varity of air flow is transfered into voltage for piezoelectric translator, and the piezoelectric ceramics will be drived to move to the focus range. Because the air pressure in nozzle flapper is related with detection distance, and the air flow is more sensitive than pressure, hotwire probe is used to detect the varity of air flow. The result shows that the accuracy of the measurement system can reach 100 nm, frequency response can come to 20 Hz, the measuring range can be 20 μm. Within a certain range, the detection distance has quite good linear relation with the varity of air flow.