Objective <p>Proprotein convertase subtilisin/kexin type 9 (PCSK9) regulates cholesterol metabolism, vascular inflammation, plaque formation, atherosclerosis, and renal injury. This study aimed to investigate the level of serum PCSK9 and its association with clinical characteristics and particularly major adverse cardiovascular event (MACE) risk in hemodialysis patients.</p> Methods <p>A Sum of 177 hemodialysis patients and 50 healthy subjects was included in this study. Serum PCSK9 level was determined by enzyme-linked immunosorbent assay. MaCE information is collected in hemodialysis patients with a median follow-up period of 15.8&#xa0;months.</p> Results <p>PCSK9 level was 179.0 [interquartile range (IQR): 106.9–297.7]&#xa0;ng/mL in hemodialysis patients, which was higher than that of 121.0 (IQR: 76.1–185.1)&#xa0;ng/mL in healthy subjects (<i>P</i> &lt; 0.001). PCSK9 level was positively correlated with age (<i>r</i> = 0.202, <i>P</i> = 0.007), total cholesterol (TC) (<i>r</i> = 0.235, <i>P</i> = 0.002), and low-density lipoprotein cholesterol (LDL-C) (<i>r</i> = 0.271, <i>P</i> &lt; 0.001) in hemodialysis patients. 18.1% of hemodialysis patients experienced MACE during the follow-up; PCSK9 level was 287.8 (IQR: 167.3–441.3)&#xa0;ng/mL in cases that experienced MaCE, which was higher than that of 163.3 (IQR: 98.4–277.0)&#xa0;ng/mL in those who did not (<i>P</i> &lt; 0.001). Receiver operator characteristic curve revealed that PCSK9 level could estimate MaCE risk with area under the curve at 0.719, and the best cutoff threshold was 163.5&#xa0;ng/mL. After adjustment by four models involving different types of parameters, PCSK9 level and PCSK9 &gt; 163.5&#xa0;ng/mL independently predicted a higher MACE risk.</p> Conclusion <p>Serum PCSK9 level correlates with age, TC, and LDL-C, and predicts a higher MACE risk in hemodialysis patients, indicating its potency as a prognostic biomarker.</p>