With the developing trend of high-integration and miniaturization of CMOS image sensors (CIS), the reliability of solder joints has become a more critical issue. This work investigated the effect of BGA distribution and solder alloys on the stress concentration of a typical CIS package under thermal-cycling conditions using experimental tests and finite element analysis. The results indicate that the interfaces of solder joints at the BGA corners have serious stress concentration and lead to crack generation in the experimental test. Reducing the pitch can alleviate stress concentration. Protection solder joints can effectively lower stress concentration and decrease the failure risk of the solder joints that undertake electrical functions. When the solder alloy is SAC305, the maximum stress in the concerned BGA array is 87.28 MPa. When the solder joints are Sn63Pb37 and Sn58Bi, the max value in this area is 98.98 MPa and 46.52 MPa, respectively.