OBJECTIVE: Hypertension is a major modifiable risk factor for cardiovascular disease and premature death worldwide. Phoenixin is a newly identified neuropeptide with multiple bioactivity. However, there was no published data about phoenixin levels in hypertension. The aim of this study was to evaluate the relationship between phoenixin and hypertension. METHODS: This study was performed in 36 patients with hypertension and 36 healthy controls. Serum phoenixin-14 and phoenixin-20 levels were determined by Enzyme-Linked ImmunoSorbent Assay method. RESULTS: Serum phoenixin-14 and phoenixin-20 values were significantly lower in hypertension patients compared with the control group (p<0.001). The levels of phoenixin-14 were negatively correlated with weight (r=-0.376; p<0.005), body mass index (r=-0.407; p<0.001), systolic blood pressure (r=-0.586; p<0.001), and diastolic blood pressure (r=-0.319; p<0.01). There was a negative correlation between serum phoenixin-20 and weight (r=-0.378; p<0.005), body mass index (r=-0.383; p<0.005), systolic blood pressure (r=-0.551; p<0.001), and diastolic blood pressure (r=-0.306; p<0.01). We used receiver operating characteristic curve analyses to compare the diagnosis value of Phoenixin-14 and Phoenixin-20 levels in hypertensive patients. We found that Phoenixin-14 value is an area under the curve of 0.87 (cutoff value 404.7 ng/L, sensitivity 92%, specificity 72%) and Phoenixin-20 value is an area under the curve of 0.83 (cutoff value 209.9 ng/L, sensitivity 86%, specificity 75%). Phoenixin-14 did nearly show equally compared to phoenixin-20 in predicting hypertension. CONCLUSION: Serum phoenixin-14 and phoenixin-20 may be related to the pathogenesis of hypertension. Our findings indicated that serum phoenixin-14 and phoenixin-20 may serve as a novel biomarker for the diagnosis of hypertension.