Tumor‐derived extracellular vesicles (EVs) have attracted tremendous interest as one of the early cancer diagnostic markers. The major obstacle preventing EV‐based liquid biopsy is the efficient collection of EVs from the complex body fluid environment. This paper introduces a nanorod‐integrated microfluidic chip capable of immunoaffinity‐isolating EVs. Periodic silicon nanorod arrays in zigzag channels are prepared by nanosphere lithography. Nanorod sidewalls provide larger binding sites for antibodies, and their close interspacing to the EV sizes improves the binding probability. The fluid simulation results show that the significant increase in isolation efficiency also comes from the liquid perturbation enhanced by the particular nanorod arrangement. Under optimal operating conditions, plasma samples from patients (n = 14) with different types of cancers (hepatocellular carcinoma, colorectal cancer, and pancreatic adenocarcinoma) to the chip for EV isolation is applied. In this proof‐of‐concept study, the expression level of the epidermal growth factor receptor (EGFR) in isolated EVs is then quantified using droplet digital PCR, showing good diagnostic performance in cancer detection.