The work aims to propose a method for sample pixel edge detection of spline interpolation, so as to improve the accuracy of detecting the tightness of drug container. An improved sub-pixel edge detection method was adopted. Firstly, the shaking blurred image was recovered. After the preprocessing of the recovered image, the spline interpolation sub-pixel edge detection method of the improved morphological gradient was used to improve the efficiency and accuracy to detect the container tightness. Based on that, the simulation experiment was conducted. The detection accuracy of such method was above 95%. It was very hard for the traditional method to achieve such effect. The method can solve the problem of low efficiency of traditional detection methods properly, and it can meet the actual detection needs.