piwi-interacting RNAs (piRNAs) are valuable biomarkers, but functional studies are still very limited. Recent research shows that piRNA-mediated cleavage acts on Transposable Elements (TEs), messenger RNAs (mRNAs), and long non-coding RNAs (lncRNAs). This study aimed to predict cancer-associated piRNA-mRNA and piRNA-lncRNA interactions as well as piRNA regulatory functions. Four cancer types (BRCA, HNSC, KIRC, and LUAD) were investigated. Interactions were identified by integrated analysis of the expression and sequence data. For the expression analysis, only piRNA–mRNA and piRNA–lncRNA pairs with expression profiles that were significantly inversely correlated were retained to reduce false-positive rates during the prediction. For the sequence analysis, miRanda was used for the target prediction. We identified 198 piRNA–mRNA and 10 piRNA–lncRNA pairs. Unlike mRNA and lncRNA expressions, the piRNA expression was relatively consistent across the cancer types. Furthermore, the identified piRNAs were consistent with previously published cancer biomarkers, such as piRNA-36741, piR-21032, and piRNA-57125. More importantly, predicted piRNA functions were determined by constructing an interaction network, and piRNA targets were placed in gene ontology categories related to the cancer hallmarks “activating invasion and metastasis” and “sustained angiogenesis”.