The PIWI-like protein 1 (PIWIL1) plays a crucial role in stem cell proliferation, embryogenesis, growth, and development, as well as differentiation and maturation in multiple organisms. The relationships between PIWIL1 expression and clinicopathological features of colorectal cancer (CRC) patients were analyzed by us. Survival analysis was performed using the Kaplan-Meier method and Cox's proportional hazards model. The high expression rate of PIWIL1 in the cancer tissue was obviously higher than that in the corresponding adjacent tissue. The expression of PIWIL1 was closely related to the tumor differentiation degree, infiltration depth, lymphovascular invasion, lymph node metastasis, and TNM stage. The Kaplan-Meier survival model suggested that the survival time of CRC patients in the high PIWIL1 expression group was notably lower than that in the low PIWIL1 expression group. High PIWIL1 expression suggests a poor prognosis for CRC patients, and PIWIL1 can serve as an important molecular marker for predicting the prognosis of CRC patients.