Background <p>PCa (Prostate cancer) is the most prevalent urogenital malignancy among men. The genes APOC1(Apolipoprotein C1) and NOP16 (Nucleolar protein 16) have been associated with various types of cancer. This article aims to investigate the potential of APOC1 and NOP16 as preliminary proactive diagnostic markers for PCa.</p> Methods <p>Search for APOC1 and NOP16 using the TCGA (The Cancer Genome Atlas) and GEPIA (Gene Expression Profiling Interactive Analysis) databases. Immunohistochemical staining was employed to detect the expression of APOC1 and NOP16 in prostate tissue. The enzyme-linked immunosorbent assay (ELISA) was utilized to quantify the levels of APOC1 and NOP16 proteins. Spearman correlation coefficient and Pearson correlation coefficient were calculated to validate the association between APOC1 and NOP16. A binary logistic regression model was developed to analyze the factors that influence PCa. Predictive models for APOC1 and NOP16 and PSA, and their role in detecting PCa, were established through the construction of receiver operating characteristic (ROC) curves.</p> Results <p>APOC1 and NOP16 are up-regulated in PCa tissues, and their expressions are related with the clinical stage of PCa(<i>n</i> = 51). Furthermore, compared with individuals affected by benign prostatic hyperplasia (BPH), the expression levels of APOC1 and NOP16 in the serum of individuals affected by PCa are higher(<i>n</i> = 61). Moreover, in the tissues and serum of the same PCa patient, APOC1 and NOP16 are positively correlated(<i>n</i> = 32). APOC1 and NOP16 are independent influencing factors for PCa(<i>n</i> = 50). APOC1 and NOP16 showed predictive potential for PCa (<i>n</i> = 50, APOC1 AUC = 0.729, NOP16 AUC = 0.777).</p> Conclusions <p>APOC1 and NOP16 are anticipated to function as biomarkers for the early proactive diagnosis of PCa.</p>