Abstract: The invention relates to a fiber-optic wave guide sensor of aptamers having functions of in situ target enrichment and purification, and a method for detection of small molecules to realize the quantitative detection of small molecules targets based on that small molecules targets and the aptamers complementary short strand DNA competitively bind with aptamers tethered on the fiber surface. It synchronously realized specifically binding aptamers with targets and in situ target enrichment and purification of targets by modifying aptamers and solid micro extraction layer with silica fibers of the fiber-optic wave guide sensor, which can achieve the ultrasensitive and ultrahigh specific quick detection for all types of small molecule targets regardless of any signal amplification reaction based on enzyme. The detection limitation is very low with good generalizability.