Abstract A novel liquid crystal (LC) biosensor was developed for the detection of platelet-derived growth factor BB (PDGF-BB) based on the orientation changes of liquid crystals. One glass slide of the LC cell was first modified with the APTES/DMOAP ((3-aminopropyl)trimethoxysilane/N,N-dimethyl-N-octadecyl(3-aminopropyl) trimethoxysilyl chloride) self-assembled monolayer (SAM) to trigger the homeotropic alignment of LC molecules and thereby produced a black background optical image under the crossed polarized light, and then the specific aptamer of PDGF-BB was immobilized on SAM through glutaraldehyde crosslinking to construct a LC sensing substrate. In the presence of PDGF-BB, the stable triple helix structure of PDGF-BB aptamer was formed by the specific binding event and thus led to the target PDGF-BB was captured to the sensing substrate, making a visible optical change which could be observed under the crossed polarized light via the huge steric effect of the PDGF-BB on disrupting the LC alignment. However, in the absence of PDGF-BB, the low packing density of the PDGF-BB aptamer had little effect on disrupting the ordered alignment to the LC and caused the black background optical image which could also be observed under the crossed polarized light. An obvious optical change was observed when the concentration of target PDGF-BB was 5 nM. The proposed LC biosensing method permits the label-free detection of PDGF-BB with good selectivity and high sensitivity, making them sufficiently simple and particularly useful for low-cost screening bioassay performed away from central laboratories.