In order to study the effect of different lithological manufactured sands on the performance of asphalt mixture, three types of lithological manufactured sands were selected to prepare asphalt mortar specimens. Uniaxial compression test, freeze-thaw splitting test and immersion Marshall test were used to test the structural strength and water stability of asphalt mortar specimens. The results show that: through the mineral composition test of X-ray diffractometer, the selected granite, diabase and limestone are typical acidic rocks, neutral rocks and alkaline rocks. Compared with the compressive strength of limestone asphalt mortar, the strength of granite mortar is about 2.5% lower, the strength of diabase mortar is about 12% higher. From the residual strength index, the freeze-thaw strength ratio of limestone mortar is the highest, but from the perspective of splitting strength before and after freeze-thaw, the tensile strength level of diabase mortar is higher. The results of the water-immersed Marshall test of the three types of manufactured sand also show the same law. Compared with conventional limestone manufactured sand, neutral rock diabase manufactured sand has better material strength and asphalt adhesion. The prepared asphalt mortar has better compressive strength and water stability, and it has good asphalt pavement engineering application value.