The aim of this investigation was to evaluate the clinical significance of the various optional surgical approaches for giant and irregular pituitary adenomas and to summarize the optimal surgical protocols for the adenomas in terms of different growth morphologies. Fifty-four cases with giant and irregular pituitary adenomas were treated by studying their clinical features and image examinations, designing the specific surgical protocols, and choosing the optimal approaches according to the various growth morphologies. Neuro-endoscope and neuronavigation-assisted techniques were applied intraoperatively. Postoperative MRI and endocrine function were re-examined routinely to judge the therapeutic efficacy of various single approaches, combined approaches and staged operations. Application of the six protocols resulted in total removal of the tumours in 18 cases, subtotal removal in 28 cases, partial removal in five cases and three deaths. The most appropriate surgical approaches, which were adopted after comprehensive analyses of the morphological characteristics presented in image examinations, those involving anatomical spaces and the clinical symptoms, can achieve the improved therapeutic results and reduce injuries to the vital anatomic structures. The tumour removal rate can be increased with the help of neuro-endoscope, neuronavigation techniques and intraoperative MRI.