Resistant hypertension is always fount to be accompanied with obstructive sleep apnea syndrome (OSAS). Previous studies assumed inflammation participated in OSAS and hypertension. The fact that tumor necrosis factor a (TNF-alpha) was related to OSAS, while neuropeptide Y (NPY) was related to hypertension, was widely reported separately. To investigate the involvement of TNF-alpha and NPY simultaneously in hypertension accompanied with OSAS, 417 subjects who underwent the polymonograph and blood pressure measurement were consecutively selected. Plasma TNF-alpha and NPY levels were determined in normotensive with OSAS (n = 113), hypertensive without OSAS (n = 73), hypertensive with OSAS (n = 134), and those of controls (n = 97), respectively. A significant increase of plasma TNF-alpha and NPY were both observed in hypertensive subjects with or without OSAS, the highest level of TNF-alpha and NPY were in hypertension with the OSAS group. TNK-alpha, NPY, and neck circumference contributed to OSAS and hypertension as risk factors in the logistic regression model. Neck circumference was impacted by apnea/hyponea index, mean diastolic blood pressure, and TNF-alpha level, which was indicated via the multiple linear model. The present study indicated a positive interplay between plasma TNF-alpha, NPY, hypertension, and OSAS in the Han population of Xinjiang. Although there is evidence that inflammation plays a role in the pathophysiology of hypertension and OSAS, clear evidence is still lacking, and raises the dilemma of the hen and the egg. Further studies are needed to clarify the role of inflammation in the pathogenesis of hypertension with OSAS, in which neck size should be considered as a linked independent factor.