<p>piRNAs could be used as biomarkers for cancer, as they are connected to progression and drug resistance in gastrointestinal cancer. Our goal is to study the expression of piR-1077 in gastric cancer and its effect on the prognosis of HER2-positive gastric cancer patients treated with trastuzumab. piRNA associated with gastric cancer was identified using piRPheno 2.0 database. We further measured the expression of identified piRNA in individuals with gastric cancer. The results showed that the development of gastric cancer was linked to piR-1077, which showed significantly elevated levels in patients (P &lt; 0.05). Further clinical data analysis found that high piR-1077 expression in gastric juice was significantly correlated with tumor size, TNM stage, lymph node metastasis, and the gastrointestinal disease marker CA724 (P &lt; 0.05). The results from the survival curve revealed that patients with high piR-1077 expression had unfavorable overall survival outcomes (P &lt; 0.05). For HER2-positive gastric cancer, up-regulation of piR-1077 expression was significantly associated with advanced malignant progression and poor prognosis (P &lt; 0.05), as well as significantly associated with trastuzumab resistance (P &lt; 0.05). In conclusion,&#xa0;piR-1077 could serve as a potential biomarker for predicting the prognosis and clinical outcomes of HER2-positive gastric cancer patients treated with trastuzumab.</p>