Fluorination of building block molecules is one of the effective engineering approaches to modulate molecular assembly in crystalline organic materials. Herein, we constructed a hydrogen-bonded organic framework (HOF) from a tetraphenylethene derivative, F-CBPE, possessing 3,5-difluoro-4-carboxyphenyl groups. The introduction of fluorine atoms in ortho-positions of the carboxy group makes the conformation of the arms more twisted, resulting in a framework structure different from that formed wit