The semiconductor plants on the top of high-tech industrial chain hire many packaging workers to carry out miscellaneous packing tasks for various product orders from different companies and countries. Under tremendous workload the quality of life (QoL) of such packaging workers need to be concerned. The aim of this study was to explore factors influencing their QoL. This study recruited 247 packing workers (162 male and 85 female; mean age: 35.6 years old) in 2015 and 2016 from a semiconductor plant in Taiwan by convenience sampling. The questionnaire comprised four parts: demographics, the World Health Organization Quality of Life (WHOQOL-BREF), an occupational burnout inventory and the Nordic Musculoskeletal Questionnaire. The four domains of the WHOQOL-BREF were defined as outcome variables. Predictive factors included gender (reference: male), age (reference: ≤ 35), BMI (reference: ≤ 25), educational level (reference: below university), marital/partner status (reference: married/cohabiting), years of work (reference: ≤ 5), work shift (reference: day shift), personal burnout, work-related burnout, over-commitment to work and the number of body parts with discomfort (0–9). The findings showed that physical QoL was negatively correlated with night -shift work, personal burnout, and number of body parts with discomfort. Psychological QoL was negatively correlated with night shift work and personal burnout. Environment QoL was negatively correlated with being male, night shift work and personal burnout. The results showed that the QoL among the packaging workers could be improved by reducing musculoskeletal discomfort, personal burnout and by improving work schedules.