Photocatalytic fuel cell (PFC) synergizes photocatalytic degradation of organic pollutants and fuel cell electrochemical reaction to take advantage of the chemical energy stored in the compounds. Herein, we report a novel 3D structured NiFe-layered double hydroxide (LDH)/BiVO4 photoanode and Cu2O-based photocathode for enhancing the efficiency of PFC for the first time. The photoanode was synthesized via a facile hydrothermal and microwave-assisted hydrothermal approach. The experimental results show that the photocurrent density and light harvesting of the PFC increase significantly. The enhanced performance is attributed to the formation of heterojunction at the photoanode resulting in reduction in the interface charge carrier recombination at the NiFe-LDH/BiVO4 junction and lower bandgap energy compared with bare BiVO4. The photocurrent density of the NiFe-LDH/BiVO4 is 90% higher than that of bare BiVO4 using Na2SO3 as the hole scavenger for substrate and 1 M phosphate buffer solution as the supporting electrolyte. The enhanced BiVO4 works as an efficient photoanode in PFC. The open-circuit voltage, short-circuit current and actual maximum power density of the NiFe-LDH/BiVO4-Cu2O/Cu PFC are 0.647 V, 0.196 mA cm−2 and 74 µW cm−2, respectively. The good performance demonstrates that the PFC is a promising technology for wastewater treatment in an eco-friendly, low-cost manner.