Objective <p>The Polo-like kinase (PLK) family contains five members, among which the former (PLK1-4) has prognostic value in colorectal cancer (CRC); however, since PLK5 was recently discovered, its related information is scarce. This study aimed to investigate the expression of PLK5 in CRC tissues versus adjacent nontumor tissues and its correlation with the characteristics and prognosis of CRC patients.</p> Methods <p>PLK5 expression was detected in 107 CRC tissues and 20 adjacent nontumor tissues via immunohistochemistry. CRC patient characteristics, relapse-free survival (RFS), and overall survival (OS) information were acquired. The Human Protein Atlas database was used for verification of the correlation of PLK5 with OS.</p> Results <p>PLK5 expression was lower in CRC tissues than in adjacent nontumor tissues (<i>P</i> &lt; 0.001); specifically, 15.0% of patients had positive PLK5 expression in tumors, and 4.7% of patients had high PLK5 expression in tumors. PLK5 expression was negatively correlated with poorly differentiated or undifferentiated tumors (<i>r</i>=-0.312, <i>P</i> = 0.001) but not with other patient characteristics. RFS tended to be greater in the PLK5-positive group than in the PLK5-negative expression group (<i>P</i> = 0.077) and in the PLK5-high-expression group than in the PLK5-low-expression group (<i>P</i> = 0.167), but the difference did not reach statistical significance. OS revealed similar trends (<i>P</i> = 0.220 and <i>P</i> = 0.264). The Human Protein Atlas database revealed that high PLK5 expression was correlated with longer OS in the rectum adenocarcinoma (TCGA) cohort (<i>P</i> = 0.037) and tended to be associated with better OS in the colon adenocarcinoma (validation) cohort (<i>P</i> = 0.120) and the rectum adenocarcinoma (validation) cohort (<i>P</i> = 0.150).</p> Conclusion <p>PLK5 is a potential tumor-suppressor biomarker for CRC management.</p>