<p>This study presents a two-dimensional photonic crystal nanocavity biosensor design that incorporates holes within a silicon slab to detect the hemoglobin concentration in blood. Since the refractive index of blood varies linearly with hemoglobin concentration, examining samples with different refractive indices enables accurate quantification of hemoglobin levels. The performance of the sensor is evaluated using the finite-difference time-domain (FDTD) method to observe resonance wavelength shifts at the output port for different blood analytes. Additionally, the photonic band structure is examined through the plane-wave expansion (PWE) method. Variations in the refractive indices of blood components result in corresponding shifts in resonant wavelength and output power. The sensor is designed to precisely measure and monitor hemoglobin concentration for clinical and diagnostic applications while maintaining a simplified fabrication process for enhanced efficiency and cost-effectiveness. The proposed device demonstrates excellent sensing performance, with a high sensitivity of 789.5 nm/RIU, a high quality factor of 1.5254<InlineEquation ID="IEq1"> <EquationSource Format="TEX">\(\times\)</EquationSource> <EquationSource Format="MATHML"><math> <mo>×</mo> </math></EquationSource> </InlineEquation>10<InlineEquation ID="IEq2"> <EquationSource Format="TEX">\(^\textrm{5}\)</EquationSource> <EquationSource Format="MATHML"><math> <mmultiscripts> <mrow /> <mrow /> <mtext>5</mtext> </mmultiscripts> </math></EquationSource> </InlineEquation>, a low detection limit of 1.282<InlineEquation ID="IEq3"> <EquationSource Format="TEX">\(\times\)</EquationSource> <EquationSource Format="MATHML"><math> <mo>×</mo> </math></EquationSource> </InlineEquation>10<InlineEquation ID="IEq4"> <EquationSource Format="TEX">\(^{-6}\)</EquationSource> <EquationSource Format="MATHML"><math> <mmultiscripts> <mrow /> <mrow /> <mrow> <mo>-</mo> <mn>6</mn> </mrow> </mmultiscripts> </math></EquationSource> </InlineEquation> RIU, and an impressive figure of merit of 7.80065<InlineEquation ID="IEq5"> <EquationSource Format="TEX">\(\times\)</EquationSource> <EquationSource Format="MATHML"><math> <mo>×</mo> </math></EquationSource> </InlineEquation>10<InlineEquation ID="IEq6"> <EquationSource Format="TEX">\(^\textrm{4}\)</EquationSource> <EquationSource Format="MATHML"><math> <mmultiscripts> <mrow /> <mrow /> <mtext>4</mtext> </mmultiscripts> </math></EquationSource> </InlineEquation> RIU <InlineEquation ID="IEq7"> <EquationSource Format="TEX">\(^\mathrm{-1}\)</EquationSource> <EquationSource Format="MATHML"><math> <mmultiscripts> <mrow /> <mrow /> <mrow> <mo>-</mo> <mn>1</mn> </mrow> </mmultiscripts> </math></EquationSource> </InlineEquation>. The device demonstrates reliable performance throughout temperatures ranging from 0 to 90 <InlineEquation ID="IEq8"> <EquationSource Format="TEX">\(^{\circ }\)</EquationSource> <EquationSource Format="MATHML"><math> <mmultiscripts> <mrow /> <mrow /> <mo>∘</mo> </mmultiscripts> </math></EquationSource> </InlineEquation>C. Furthermore, considering the susceptibility of photonic crystal structures to fabrication imperfections, the study includes an in-depth evaluation of their impact on sensor performance to ensure reliability in real-world applications. With its compact footprint of 95.48 <InlineEquation ID="IEq9"> <EquationSource Format="TEX">\(\mu \text {m}^2\)</EquationSource> <EquationSource Format="MATHML"><math> <mrow> <mi>μ</mi> <msup> <mtext>m</mtext> <mn>2</mn> </msup> </mrow> </math></EquationSource> </InlineEquation> and excellent sensing capabilities, the proposed biosensor is well-suited for label-free medical diagnostics and photonic integrated circuits.</p>