In lithography, peeling and collapse of photoresist patterns cause difficulties of micro fabrication. In order to prevent the destructions, enhancement of adhesion between the photoresist and substrate is effective. Therefore, significance of accurate adhesion analysis increases with miniaturization of device process. The destructions of photoresist/substrate interface can be mainly categorized into interfacial and cohesive failures. In this study, we propose the direct analysis of adhesion in nanoscale area. Using AFM, we estimate adhesion energy of AFM-tip/Si interface in local area and identify the destruction mode of photoresist/Si interface. First, we evaluates the adhesion between photoresist films and surface modified Si substrates. From the surface free energy analysis, the threshold adhesion work, 𝑊𝐴𝑡ℎ (J/m2) of photoresist/Si interface is estimated to be 71.7 mJ/m2 in order to identify the destruction mode in macro area. Secondary, the interaction between the AFM tip and the surface modified Si substrates are evaluated in the local area less than 10 nm in diameter. The interaction energy, 𝐸𝐼 (J) of AFM-tip/Si interface shows a positive correlation with the adhesion work of photoresist/Si interface. We estimate effective area for adhesion of AFM-tip/Si and adhesion energy, 𝐸𝐴 (J/m2) of AFM-tip/Si in nanoscale area. The results predict that only interfacial destruction occurs at photoresist/Si interface when the adhesion energy of AFM-tip/Si is less than 44.7 mJ/m2. We can expect that the quantitative analysis of nanoscale adhesion contribute to improve the accuracy of nanolithography process.