We investigate the generalized Poland-Scheraga model, which is used in the bio-physical literature to model the DNA denaturation transition, in the case where the two strands are allowed to be non-complementary (and to have different lengths). The homogeneous model was recently studied from a mathematical point of view in [35, 7], via a 2-dimensional renewal approach, with a loop exponent 2 + α (α > 0): it was found to undergo a localization/delocalization phase transition-which corresponds to the denaturation transition-of order ν = min(1, α) −1 , together within generalother phase transitions. In this paper, we turn to the disordered model, and we address the question of the influence of disorder on the denaturation phase transition, that is whether adding an arbitrarily small amount of disorder (i.e. inhomogeneities) affects the critical properties of this transition. Our results are consistent with Harris' predictions for d-dimensional disordered systems (here d = 2). First, we prove that when α < 1 (i.e. ν > d/2), then disorder is irrelevant: the quenched and annealed critical points are equal, and the disordered denaturation phase transition is also of order ν = α −1. On the other hand, when α > 1, disorder is relevant: we prove that the quenched and annealed critical points differ. Moreover, we discuss a number of open problems, in particular the smoothing phenomenon that is expected to enter the game when disorder is relevant.