Objective To investigate the effect of pathologically elevated cyclic strain induced by hypertension on proliferation of vascular smooth muscle cells (VSMCs) and the role of long non-coding RNA (IncRNA)-XR007793 during this process. Methods Flexcell-4000 tension system was used to apply physiologically (5% magnitude) and pathologically (15% magnitude) cyclic strain with frequency of 1.25 Hz on VSMCs for 24 h respectively. qRT-PCR was used to detect the expression of XR007793 and 4 co-expressed genes: signal transducer and activator of transcription 2 (STAT2), cell division cycle associated 8 (CDCA8), proto-oncogene LMO2 and interferon regulatory factor (IRF7). Western blot was used to detect the proliferating cell nuclear antigen (PCNA) level in VSMCs. RNA inference was used to inhibit XR007793 expression. The cell cycle of VSMCs was measured by flow cytometry in static condition and the cell proliferation was detected by Brdu-Elisa in cyclic strain loading condition. Results Compared with 5% cyclic strain, 15% cyclic strain remarkably decreased the XR007793 level and increased the proliferation of VSMCs，along with the increasing expression of STAT2 and CDCA8. XR007793 specific siRNA transfection under static condition decreased the expression of XR007793 and increased the VSMC proliferation. Under 15% cyclic strain, XR007793 specific siRNA transfection also increased the VSMC proliferation and the expression of CDCA8 compared with the non-specific siRNA control. Conclusions Pathologically elevated cyclic strain decreases the XR007793 expression level and increases the CDCA8 expression level to modulate VSMC proliferation. These results provide new experimental evidence for the study of mechanobiological mechanism during hypertension and potential targets for hypertension therapy.