The processing of bioproducts and food often requires efficiently separating particles such as mammalian or yeast cells from solutions. The rapid growth of biotechnology and food sectors has attracted increasing attention to exploring hydrocyclones as efficient separation instruments because they can operate continuously at high throughput with low capital and operational costs. This review summarizes their emerging applications in food and bioproduct processing. While hydrocyclones are efficient in removing larger particles such as mammalian cells, separating small cells such as yeast is more challenging. To tackle such challenges, combining strategies such as decreasing body diameters and increasing inlet velocities has been explored at the cost of increasing the water split at underflow and reducing the concentration ratio. To help obtain a high concentration ratio and achieve satisfactory removal efficiency, we review valuable measures such as non-standard unit design, geometry and operation optimization, and integration of hydrocyclones with microfluidic particle-sorting techniques. Important tools, including artificial intelligence methods and 3-D printing technologies, are discussed for the rapid design and test of hydrocyclones. Emerging applications and challenges, e.g., the integration of hydrocyclone with perfusion bioreactor and cell disruption, are reviewed.