The recently discovered 12442-type iron-based superconductors (IBSs), ACa2Fe4As4F2 (A = K, Rb, Cs), are intrinsically self-hole doped stoichiometric compounds that exhibit superconductivity with Tc = 30–33.5 K. In this paper, single crystals of Ni doped RbCa2(Fe1−xNix)4As4F2 with 0 ⩽ x ⩽ 0.1 have been successfully grown for the first time using a RbAs flux method and characterized by energy dispersive x-ray spectroscopy (EDS), x-ray diffraction (XRD), electrical resistivity, magnetic susceptibility, and Hall effect measurements. EDS and XRD measurements suggest that the Ni dopants are successfully doped into the crystal lattice. Based on the electrical resistivity and magnetization data, we construct the Tc–x phase diagram. Furthermore, it is found that Ni dopants not only introduce extra electrons that modify the topology of Fermi surface, but also act as impurity scattering centers that contribute to the pair breaking effect, i.e., the superconducting transition temperature Tc is suppressed with a rate of ΔTc/Ni-1% = −2.7 K. Intriguingly, such suppression of Tc and those in other similar hole doped IBSs, such as Ba0.6K0.4Fe2As2, Ba0.5K0.5Fe2As2, and EuRbFe4As4 with multiple nodeless gaps, can be well scaled together. Combining with relevant experimental data reported so far, we speculate that the pairing symmetry in 12442 system is very likely to be nodeless s±-wave. Finally, doping evolution of the upper critical field and its anisotropy are investigated and discussed in detail. Upon Ni doping, the coherence length ξc(0) is gradually increased and becomes larger than the FeAs interbilayer distance when x > 0.07, indicating that the nature of superconductivity changes from quasi two-dimensional (2D) to three-dimensional (3D). The anisotropy of the upper critical field γH close to Tc shows a nonmonotonic dependence on doping, which first increases from 6.7 at the pristine sample to its maximum 8.1 at x = 0.03, and then decreases to 3.7 at x = 0.09.