The self-adjointness of Δ2 + κ|x|−4 (κ>κ0 = κ0(N)) in L2(ℝN) is established as an application of the perturbation theorem in terms of Re(Au, Bεu), u ∈ D(A), for two non-negative self-adjoint operators A, B in a Hilbert space, where the family {Bε}ε>0 is the Yosida approximation of B. A key to the proof lies in a new inequality for the functions ν ∈ L2(ℝN) with |x|2Δν ∈ L2(ℝN) derived by using two real parameters.