import pandas as pd df1 = pd.DataFrame({'A': [1, 2, 3, 4], 'B': ['a', 'b', 'c', 'd']}) df2 = pd.DataFrame({'A': [2, 4], 'B': ['b', 'd']}) mask = df1.isin(df2.to_dict('list')).all(axis=1) filtered_df = df1[~mask] print(filtered_df)