Crude oil stored in large storage tanks for a long period produces sludge at the bottom of the tank, seriously affecting the safe operation of the tank. In order to improve the efficiency of sludge cleaning in crude oil storage tanks, taking the oil storage tank sludge of Shenxian oil transmission station as an example, the cleaning agent SDQ-1 was preferred based on the results of sludge property testing. The influence of additive concentration, temperature, oscillation rate, and cleaning time on the sludge cleaning effect were then analyzed. In addition, the dissolution mechanism of sludge was investigated through molecular dynamics simulation. The studies showed that the sludge contained more than 95% oil, and the main components were paraffins and asphaltenes. Under the reaction conditions of dosing concentration of 0.06 g/mL, temperature of 45 ℃, oscillation rate of 250 r/min, and cleaning time of 4 hours, the dissolution rate of diluted oil to sludge was enhanced by 31.59% as compared with that without dosing, and the dissolution rate was 2.36×10-3 g/min. The results of molecular simulation also confirmed that the methylphenethyl ether in the cleaning agent SDQ-1 could promote the dissolution of asphaltenes in sludge, and that methylphenethyl ether and kerosene synergistically promoted the dissolution of paraffins in the sludge. Therefore, the research results provide significant reference for the selection of optimal cleaning agent to improve the efficiency of sludge cleaning in crude oil storage tanks.