Clinical non-functioning pituitary adenoma (NFPA) accounts for >30% of all pituitary adenomas, and the recurrence rate is notably high. The ability to predict tumour recurrence during initial surgery will aid in determining if adjunctive therapy is required to reduce recurrence. With the aim of developing a circular RNA (circRNA) signature to improve prognosis prediction in NFPA, the present study examined the circRNA expression profiles in 73 patients with NFPA from Beijing Tiantan Hospital using high-throughput RNA chip technology. The dataset was randomly separated into a training group and a test group using an R program. In the training group (n=37), a Cox proportional hazards regression model was used to analyse the genes associated with the recurrence and progression-free survival (PFS) of patients with NFPA. Meanwhile, a random survival forest algorithm, Kaplan-Meier and receiver operating characteristic curve (ROC) analyses were used to determine the multi-circRNA signature with the largest area under the ROC curve (AUROC) and verify its efficacy in the test group (n=36). In the training and test groups, the signatures of two circRNAs (hsa_circ_0000066 and hsa_circ_0069707) were specifically associated with the PFS of patients with NFPA (log-rank P<0.05). Furthermore, the two-circRNA signature had a high prediction accuracy for tumour recurrence, with an AUROC of 0.87 and 0.67 in the training and test groups, respectively; and the discriminative power of the signature was greater compared with that of age. The present study is the first to suggest a circRNA signature with a clinical application value for predicting recurrence/progression in patients with NFPA.