This work reports influences of variation in Ni-doping on structural, morphological, and optical properties of CdS thin films and in their hybrid solar cell applications. X-ray diffraction data showed that increase of Ni-doping in CdS structure caused not only a broadening in CdS peak but also a decrease in the intensity of main cubic CdS peak. Morphological studies illustrated that lower amount of Ni-doping treatment firstly reduced the grain size of CdS thin films, whereas higher concentration of Ni-doping led to bigger grains. The best transparent CdS sample was achieved for 1 at% Ni-doping as 95% at 675 nm. Compared with CdS thin films (2.98 eV), bandwidths of Ni-doped CdS samples gradually increased and reached to 3.39 eV, which is due to the existence of strong quantum confinement effect. Photoluminescence (PL) data of the device demonstrated that the most efficient electron transfer was accomplished at CdS/P3HT interface for 1 at% Ni-doping because this device demonstrated the lowest PL peak intensity. Current density-voltage (J-V) characteristics of CdS-based device exhibited a power conversion efficiency (PCE) of 0.296% and it enhanced to 0.663% for device including 1 at% Ni atoms, which is most probably due to achievement of most efficient exciton dissociation between CdS and P3HT layers as approved by PL results. However, with increasing Ni-doping amount up to 3 at% and 5 at%, PCE values were in turn obtained as 0.131% and 0.208%, indicating a deterioration in PCE value of cells, which might be due to the less efficient exciton dissociation at the interface. Further increase of Ni-doping to 7 at% led to an efficiency value of 0.417%, which is still lower than that of 1 at% Ni-doped CdS-based device.