In this article, a hybrid TiO2/Au/graphene layer-based surface plasmon resonance (SPR) sensor with improved sensitivity and capability for cancer detection is presented. The finite element method (FEM) was used for numerical analysis. The proposed SPR biosensor was structured based on the angular analysis of the attenuated total reflection (ATR) method for the detection of various types of cancer using the refractive index component. The resonance angle shifted owing to the increment of normal and cancerous cells’ refractive index, which varied between 1.36 and 1.401 for six different types of normal and cancerous cells. According to numerical results, the obtained sensitivities for skin (basal), cervical (HeLa), adrenal gland (PC12), blood (Jurkat), and breast (MCF-7 and MDA-MB-231) cancer cells were 210 deg/RIU, 245.83 deg/RIU, 264.285 deg/RIU, 285.71 deg/RIU, 292.86 deg/RIU, and 278.57 deg/RIU, respectively. Furthermore, the detection accuracy (DA), figure of merits (FOM), and signal-to-noise ratio (SNR) were also obtained, with values of 0.263 deg−1, 48.02 RIU−1, and 3.84, respectively. Additionally, the distribution of the electric field and the propagation of the magnetic field for resonant and non-resonant conditions of the proposed structure were illustrated. It was found that an enhanced field was exhibited on the surface of the plasmonic material for resonant conditions. We also measured the penetration depth of 180 nm using decayed electric field intensity. Furthermore, the impact of using a TiO2/Au/graphene layer was demonstrated. We further conducted analyses of the effects of the thickness of the gold layer and the effects of additional graphene layers on overall sensitivities for six different types of cancer. The proposed TiO2/Au/graphene layered structure exhibited the highest overall sensitivity in terms of detecting cancerous cells from healthy cells. Moreover, the proposed sensor was numerically analyzed for a wide range of biological solutions (refractive index 1.33 –1.41), and the sensor linearity was calculated with a linear regression coefficient (R2) of 0.9858. Finally, numerical results obtained in this manuscript exhibited high sensitivity in comparison with previously reported studies.