Photoconductive organic materials have gained increasing interest in various optoelectronics, such as sensors, photodetectors, and photovoltaics. However, the availability of such materials is very limited due to their intrinsic low charge carrier density and mobility. Here, we present a simple approach based on nanofibril heterojunction to achieve high photoconductivity with fast photoresponse, that is, interfacial engineering of electron donor (D) coating onto acceptor (A) nanofibers via optimization of hydrophobic interaction between long alkyl side-chains. Such nanofibril heterojunctions possess two prominent features that are critical for efficient photocurrent generation: the nanofibers both create a large D/A interface for increased charge separation and act as long-range transport pathways for photogenerated charge carriers toward the electrodes, and the alkyl groups employed not only enable effective surface adsorption of D molecules on the nanofibers for effective electron-transfer communication, but also spatially separate the photogenerated charge carriers to prevent their recombination. The reported approach represents a simple, adaptable method that allows for the development and optimization of photoconductive organic materials.