For 6D, N = (1, 1) SYM theory formulated in N = (1, 0) harmonic superspace as a theory of interacting gauge multiplet and hypermultiplet we construct the N = (1, 1) supersymmetric Heisenberg-Euler-type superfield effective action. The effective action is computed for the slowly varying on-shell background fields and involves, in the bosonic sector, all powers of a constant abelian strength.Note that 6D, N = (1, 1) SYM theory is non-renormalizable by power counting. However, it was found that this theory is on-shell finite at one and two loops [28], [29], [30], [31], [32], [33], [34], [35]. Recently, the aspects of renormalizability of the theory under consideration were studied by harmonic superspace techniques. It was shown that there is a gauge choice at which the one-loop divergences are completely canceled off shell [25], [26], [27]. Some two-loop harmonic supergraphs are also finite [36] 4 .1 These results were recently confirmed by the component calculations in [9]. 2 The relationships of the 6D, N = (1, 1) SYM theory with the low-energy dynamics of D5 branes are discussed in [14], [15], [16].3 Review of various applications of the background harmonic superfields for studying the effective actions of 4D, N = 2, 4 SYM theories was given in [6], [7]. 4 Gauge dependence of the one-loop divergences was studied in [37].