Inertial microfluidics has drawn much attention for its applications for circulating tumor cell separations from blood. The fluid flows and the inertial particle focusing in inertial microfluidic systems are highly dependent on the channel geometry and structure. Flexible microfluidic systems can have adjustable 3D channel geometries by curving planar 2D channels into 3D structures, which will enable tunable inertial separation. We present a poly(dimethylsiloxane) (PDMS)-parylene hybrid thin-film microfluidic system that can provide high flexibility for 3D channel shaping while maintaining the channel cross-sectional shape. The PDMS-parylene hybrid microfluidic channels were fabricated by a molding and bonding technique using initiated chemical vapor deposition (iCVD) bonding. We constructed 3D helical inertial microfluidic channels by coiling a straight 2D channel and studied the inertial focusing while varying radius of curvature and Reynolds number. This thin film structure allows for high channel curvature and high Dean numbers which leads to faster inertial particle focusing and shorter channel lengths than 2D spiral channels. Most importantly, the focusing positions of particles and cells in the microchannel can be tuned in real time by simply modulating the channel curvature. The simple mechanical modulation of these 3D structure microfluidic systems is expected to provide unique advantages of convenient tuning of cell separation thresholds with a single device.