Prostate cancer (PCa) is the most common cancer affecting men, with increasing global mortality and morbidity rates. Despite the progress in the diagnosis and treatment of PCa, patient outcomes remain poor, and novel therapeutic targets for PCa are urgently needed. Recently, circular RNAs (circRNAs) have been studied in-depth as potential biomarkers for many diseases. In this study, circRNA microarrays using four pairs of PCa tissues were utilized to show that circGFRA1 was upregulated in PCa tumor tissues. CircGFRA1 is suggested to play an oncogene role in PCa progression as the silencing of circGFRA1 inhibited the proliferation, migration, and immune escape activity of PCa cells. Furthermore, by utilizing bioinformatics analysis, RIP, RNA pull-down, and luciferase reporter assays, our results showed that LMX1B could bind to the GFRA1 promoter and regulate circGFRA1 expression in PCa cells and circGFRA1 upregulated HECTD1 expression through sponging miR-3064-5p. This novel LMX1B/circGFRA1/miR-3064-5p/HECTD1 axis identified in PCa provides new insights for developing novel therapeutic strategies for PCa.