Titanomagnetite occurs commonly in igneous and metamorphic rocks, and various types of deposits, and serves as a valuable indicator. Recently, it has been identified as a new geochronometer for U–Pb dating. However, no reference material is available currently. Thus, we used a titanomagnetite sample HG79c with a known age of 259.2 ± 2.8 Ma to evaluate potential primary standards and establish an accurate calibration method for widespread application. In our in situ U–Pb dating experiments, different ablation settings were optimized, i.e., spot sizes of 44 and 60 μm, laser frequencies of 6, 8, and 10 Hz, and energy densities of 3, 4, and 8 J cm⁻². 3 ml min⁻¹ nitrogen was introduced to enhance sensitivity and reduce matrix effects. Five Concordia-intercept ²⁰⁶Pb/²³⁸U ages were obtained for HG79c using cassiterite AY-4 as an external standard, and four are consistent with or slightly younger than the reference age within errors. Two accurate ages were obtained when HG79c was calibrated by zircon 91500 and garnet PL-57. All these age results and Pb/U fractionation confirm that cassiterite and zircon have a normalized Pb/U ratio consistent with titanomagnetite in some optimized ablation settings. We utilized cassiterite AY-4 as the primary standard, HG79c as quality control in an optimized ablation setting, i.e., a spot size of 60 μm, energy density of 4 J cm⁻², and laser frequency of 6 Hz, to date titanomagnetite LL22-137 from the Lala Fe–Cu deposit in the Kangdian IOCG metallogenic province, China. This titanomagnetite yielded a Concordia-intercept ²⁰⁶Pb/²³⁸U age of 853.2 ± 9.9 Ma, which agrees well with the intergrown rutile U–Pb age of 850.8 ± 8.7 Ma and the published U–Pb ages for apatite and secondary allanite, and Re–Os age for molybdenite from the same deposit. This method offers a new tool for directly dating diagenesis and ore-forming processes related to Fe and Ti metals.