Chiral interactions are prevalent in nature, driving a variety of bio-chemical processes. Discerning the two non-superimposable mirror images of a chiral molecule, known as enantiomers, requires interaction with a chiral reagent with known handedness. Circularly polarized light beams are often used as a chiral reagent. Here, we demonstrate efficient chiral sensitivity with linearly polarized helical light beams carrying an orbital angular momentum of ±lh, in which the handedness is defined by the twisted wavefront structure tracing a left-or right-handed corkscrew pattern as it propagates in space. By probing nonlinear optical response, we show that helicity dependent nonlinear absorption occurs even in achiral molecules and can be precisely controlled. We model this effect by considering induced multipole moments in light-matter interactions. Design and control of light-matter interactions with helical light opens new opportunities in chiroptical spectroscopy, light-driven molecular machines, optical switching, and in-situ ultrafast probing of chiral systems and magnetic materials.