The self-affine measure μ M,D corresponding to an expanding matrix M ∈ M n (R) and a finite subset D ⊂ R n is supported on the attractor (or invariant set) of the iterated function system {φ d (x) = M −1 (x + d)} d∈D . The spectral and non-spectral problems on μ M,D , including the spectrum-tiling problem implied in them, have received much attention in recent years. One of the non-spectral problem on μ M,D is to estimate the number of orthogonal exponentials in L 2 (μ M,D ) and to find them. In the present paper we show that if a, b, c ∈ Z, |a| > 1, |c| > 1 and ac ∈ Z \ (3Z),then there exist at most 3 mutually orthogonal exponentials in L 2 (μ M,D ), and the number 3 is the best. This extends several known conclusions. The proof of such result depends on the characterization of the zero set of the Fourier transformμ M,D , and provides a way of dealing with the non-spectral problem.