We generalize the Pfaffian formalism, which has been playing an important role in the study of time-reversal invariant topological insulators (TIs), to 3D chiral higher-order topological insulators (HOTIs) protected by the product of four-fold rotational symmetry C 4 and the time-reversal symmetry T. This Pfaffian description reveals a deep and fundamental link between TIs and HOTIs, and allows important conclusions about TIs to be generalized to HOTIs. As examples, we demonstrate in the Letter how to generalize Fu-Kane's parity criterion for TIs to HOTIs, and also present a general method to efficiently compute the Z 2 index of 3D chiral HOTIs without a global gauge.Introduction.-In comparison to the well-studied topological insulators (TIs), which have a gapped d-dimensional bulk and topologically-protected gapless states on its d − 1 dimensional boundaries [1][2][3][4][5][6], the recently proposed higher-order topological insulators (HOTIs) have a similar gapped bulk, but the gapless states emerge at lower dimensions, e.g. the 1D hinge of a 3D insulator . In this Letter, we focus on second-order topological insulators characterized by nontrivial magneto-electric polarization P 3 , e.g., 3D chiral second-order topological insulators (CSOTIs) with gapless chiral hinge states propagating in alternative directions. These second-order TIs have a strong connection to TIs, and in particular, if the time-reversal symmetry T is enforced, 2P 3 recovers the Z 2 index of a TI [30]. If the time-reversal symmetry is broken, 2P 3 still defines a Z 2 topological index, as long as a space inversion, rotoinversion or C n T symmetry is preserved [7][8][9][10][11][12][13][14][15], where C n represents n-fold rotation with n = 2, 4, 6, and this Z 2 index, in the absence of time-reversal symmetry, characterizes a second-order TI. For systems invariant under space-inversion or some rotoinversion, this topological index is fully dictated by high-symmetry points and can be conveniently obtained using the framework of topological quantum chemistry [31] or symmetry indicators [32,33]. However, in general, calculating P 3 requires more sophisticated techniques like the nested Wilson loops [7,17,18,[34][35][36].