I think you can use Index.difference :
df[df.columns.difference(dgh_columns)]
Example:
df = pd.DataFrame({'A':[1,2,3], 'B':[4,5,6], 'C':[7,8,9], 'D':[1,3,5], 'E':[7,8,9], 'F':[1,3,5], 'G':[5,3,6], 'H':[7,4,3]}) print (df) ABCDEFGH 0 1 4 7 1 7 1 5 7 1 2 5 8 3 8 3 3 4 2 3 6 9 5 9 5 6 3 dgh_columns = pd.Index(['D', 'G', 'H']) print (df[df.columns.difference(dgh_columns)]) ABCEF 0 1 4 7 7 1 1 2 5 8 8 3 2 3 6 9 9 5
Numpy solution with numpy.setxor1d or numpy.setdiff1d :
dgh_columns = pd.Index(['D', 'G', 'H']) print (df[np.setxor1d(df.columns, dgh_columns)]) ABCEF 0 1 4 7 7 1 1 2 5 8 8 3 2 3 6 9 9 5
dgh_columns = pd.Index(['D', 'G', 'H']) print (df[np.setdiff1d(df.columns, dgh_columns)]) ABCEF 0 1 4 7 7 1 1 2 5 8 8 3 2 3 6 9 9 5