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This paper proves a Serrin’s type blow-up criterion for the 3D density-dependent Navier-Stokes-Korteweg equations with vacuum. It is shown that if the density $\rho$ and velocity field $u$ satisfy ${\parallel \nabla \rho \parallel }_{L^{\infty }(0,T;W^{1,q})}+{\parallel u\parallel }_{L^s(0,T;L_{\omega }^r)}<\infty$ for some $q>3$ and any $(r,s)$ satisfying $2/s+3/r\le 1$, $3<r\le \infty ,$ then the strong solutions to the density-dependent Navier-Stokes-Korteweg equations can exist globally over $[0,T]$. Here $L_{\omega }^r$ denotes the weak $L^r$ space.