Currency substitution means that residents change the holdings of foreign currency due to the opportunity cost. Currently, the proportion of Pataca used for money supply (M2) is only 24.03%, and Hong Kong Dollar, RMB have gradually replaced the Pataca in Macau. Firstly, the paper uses relative indexes to measure the degree of currency substitution in Macau and shows that the degree is very high. Then the ADF Test, Cointegration Analysis, Vector Error Correct Model and Granger Causal Relation Test are used to analyze the factor of the substitution effect. The result shows that first-order lag of lucky lottery revenue, of total trade in Macau with Hong Kong and the mainland and of the Pataca exchange rate against the RMB have positive impacts on currency substitution, and the first-order lag of the currency substitution rate, of the interest margin of Pataca and RMB, of interest margin of Pataca and HK Dollar have negative impacts. Currency the substitution of the Pataca and total trade in Macau with Hong Kong and the mainland have Mutual Granger Causal Relationship, but currency substitution and the interest margin of the Pataca and HK Dollar have no Granger Causal Relationship.