Transcription factors (TFs) control an array of expressed genes. However, the specifics of how a gene is expressed in time and space as controlled by a TF remain largely unknown. Here, in TRPC6-regulated proline oxidase 1 (POX) transcription in human glioma, we report that OIP5-AS1, a long noncoding RNA, determines the specificity of p53-driven POX expression. The OIP5-AS1/p53 complex via its 24 nucleotides binds to the POX promoter and is necessary for POX expression but not for p21 transcription. An O-site in the POX promoter to which OIP5-AS1 binds was identified that is required for OIP5-AS1/p53 binding and POX transcription. Blocking OIP5-AS1 binding to the O-site inhibits POX transcription and promotes glioma development. Thus, the OIP5-AS1/O-site module decides p53-controlled POX expression as regulated by TRPC6 and affects glioma development.