MOTIVATION: Bistability is one of the salient dynamical features in various all-or-none kinds of decision-making processes. The presence of bistability in a cell signalling network plays a key role in input-output (I/O) relation. Our study is aiming to capture and emphasize the role of motif structure influencing the I/O relation between two nodes in the context of bistability. Here, a model-based analysis is made to investigate the critical conditions responsible for the emergence of different bistable protein-protein interaction (PPI) motifs and their possible applications to find the potential drug-targets. RESULTS: The global sensitivity analysis is used to identify sensitive parameters and their role in maintaining the bistability. Additionally, the bistable switching through hysteresis is explored to develop an understanding of the underlying mechanisms involved in the cell signalling processes, when significant motifs exhibiting bistability have emerged. Further, we elaborate the application of the results by the implication of the emerged PPI motifs to identify potential drug-targets in three cancer networks, which is validated with existing databases. The influence of stochastic perturbations that could hinder desired functionality of any signalling networks is also described here. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.