In order to improve the efficiency of CO₂ flooding in low permeability reservoir，the interaction between CO₂ and crude oil and the influence on CO₂ flooding were studied. Firstly，the principle of CO₂-crude oil interaction under different pressures was analyzed from two aspects such as dissolution and extraction. Then，CO₂ huff and puff experiments were carried out using the de signed core model. At the same time，nuclear magnetic resonance scan was performed on the core before and after displacement and the distribution of remaining oil was analyzed. Finally，combining with the field application in Jiangsu oilfield，the further applica tion direction of CO₂ flooding was proposed. Experiment results showed that when the pressure exceeded the threshold value（10.0 MPa），the extraction rate increased significantly with increasing pressure. The extraction rate reached 85.2% at 40.0 MPa. When the pressure was less than the oil-shrinkage value（13.0 MPa），the crude oil exhibited volume expansion with a maximum expansion co efficient of 1.25. When the pressure was greater than 13.0 MPa，the crude oil exhibited a significant volume shrinkage under the strong extraction of CO₂. The flooding experiment results showed that for a low permeability matrix core with a length of 6.0 cm， the recovery factor of CO₂ huff and puff was 48.0%. During the earlier stage of displacement，the main mechanism of increasing production was oil expansion due to the dissolution of CO₂ in crude oil. And during the second stage of displacement，light weight component extracted by CO₂ was the main factor. In practical application，the effect of oil reservoir conditions on the interaction be tween CO₂ and crude oil should be fully considered. Reservoir with pressure under 15 MPa gave priority to CO₂ huff and puff，and that above 15 MPa gave priority to CO₂ flooding.